NM_000256.3(MYBPC3):c.2827C>T (p.Arg943Ter)
Germline
Classification
Help
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
Pathogenic
Pathogenic (21)
Pathogenic (21)
21 out of 28 submissions contributed to this classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
28
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000256.3(MYBPC3):c.2827C>T (p.Arg943Ter)
Variation ID: 37039 Accession: VCV000037039.53
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p11.2 11: 47335120 (GRCh38) [ NCBI UCSC ] 11: 47356671 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Aug 4, 2026 Mar 4, 2026 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000256.3:c.2827C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000247.2:p.Arg943Ter nonsense NC_000011.10:g.47335120G>A NC_000011.9:g.47356671G>A NG_007667.1:g.22583C>T LRG_386:g.22583C>T LRG_386t1:c.2827C>T LRG_386p1:p.Arg943Ter - Protein change
- R943*
- Other names
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p.R943*:CGA>TGA
- Canonical SPDI
- NC_000011.10:47335119:G:A
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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Trans-Omics for Precision Medicine (TOPMed) 0.00000
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
The Genome Aggregation Database (gnomAD) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00001
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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| MYBPC3 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
4727 | 4749 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (9) |
criteria provided, multiple submitters, no conflicts
|
Aug 28, 2025 | RCV000030699.26 | |
| Pathogenic (9) |
criteria provided, multiple submitters, no conflicts
|
Feb 3, 2026 | RCV000158189.24 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Mar 4, 2026 | RCV000248559.4 | |
| Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Jan 13, 2026 | RCV000471886.24 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Dec 18, 2023 | RCV001179578.8 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
Expand all rows
Collapse all rows
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Feb 20, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Cardiomyopathy |
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003844999.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
Comment:
show
Variant summary: MYBPC3 c.2827C>T (p.Arg943X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 247124 control chromosomes (gnomAD). c.2827C>T has been reported in the literature in multiple individuals affected with Hypertrophic Cardiomyopathy (e.g. Van Driest_2004, Deprez_2006, Michels_2007, Berge_2013). These data indicate that the variant is very likely to be associated with disease. 15 clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
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Pathogenic
(Nov 03, 2020)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000059178.6
First in ClinVar: May 03, 2013 Last updated: Apr 20, 2024 |
Comment:
show
The p.Arg943X variant in MYBPC3 has been reported in >25 individuals with hypertrophic cardiomyopathy (HCM) and segregated with disease in 4 affected relatives in 4 families (Alders 2003 PMID: 14563344, Lekanne Deprez 2006 PMID: 16679492, Foksteun 2008 PMID: 18409188, Morita 2008 PMID: 18403758, Michels 2009 PMID: 19356534, Van Driest 2004 PMID: 15519027, Tajsharghi 2010 PMID: 19858127, Yiu 2012 PMID: 22574137, Wessels 2014 PMID: 25335496, LMM unpublished data). Several of these individuals carried an additional clinically significant variant and presented with early onset disease. This variant has been reported by other clinical laboratories in ClinVar (Variation ID 37039) and has also been identified in 0.006% (2/30444) of South Asian chromosomes by gnomAD (https://gnomad.broadinstitute.org/). This nonsense variant leads to a premature termination codon at position 943, which is predicted to lead to a truncated or absent protein. Loss of function of the MYBPC3 gene is an established disease mechanism in autosomal dominant HCM. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HCM. ACMG/AMP criteria applied: PVS1, PS4, PP1, PM2_supporting. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
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Pathogenic
(Jun 24, 2022)
C
Contributing to aggregate classification
|
criteria provided, single submitter
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Hypertrophic cardiomyopathy 4 |
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Accession: SCV005399406.1
First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024 |
Comment:
show
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with hypertrophic cardiomyopathy 4 (HCM; MIM#115197). (I) 0108 - This gene is associated with both recessive and dominant disease. Dominant inheritance is frequently reported in adult onset conditions, however recessive inheritance results in a more severe early onset phenotype (OMIM). (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 32841044). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (4 heterozygotes, 0 homozygotes). (SP) 0701 - Other null variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. There are at least ten pathogenic NMD-predicted variants that have been reported (DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant is a Dutch founder variant and has been classified as pathogenic by multiple diagnostic laboratories. This variant has also been reported to be compound heterozygous or homozygous in individuals with severe early-onset disease (ClinVar, PMID: 25335496). (SP) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) heterozygous for this variant demonstrated aberrant calcium signalling and prolonged relaxation kinetics compared to WT cells, with homozygous iPSC-CMs demonstrating more severe impairment (PMID: 30586709). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(Feb 01, 2021)
C
Contributing to aggregate classification
|
criteria provided, single submitter
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not provided
(Autosomal dominant inheritance)
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001480055.2
First in ClinVar: Feb 20, 2021 Last updated: Apr 13, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Clinical Features:
Hypertrophic cardiomyopathy (present) , Biventricular hypertrophy (present)
Sex: male
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Pathogenic
(Mar 04, 2026)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Cardiovascular phenotype |
Ambry Genetics
Accession: SCV000319955.7
First in ClinVar: Oct 02, 2016 Last updated: Apr 25, 2026 |
Comment:
show
The c.2827C>T (p.R943*) alteration, located in exon 27 (coding exon 27) of the MYBPC3 gene, consists of a C to T substitution at nucleotide position 2827. This changes the amino acid from a arginine (R) to a stop codon at amino acid position 943. This variant is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of 0.001% (3/247124) total alleles studied. The highest observed frequency was 0.007% (2/30444) of South Asian alleles. This variant was reported in individual(s) with features consistent with hypertrophic cardiomyopathy, and has been reported as a Dutch founder mutation (Van Driest, 2004; Michels, 2007; Michels, 2009; Christiaans, 2010; Brito, 2012; Hathaway, 2021). This variant has been reported as occurring in the homozygous state and also with other alterations in patients with severe, early onset disease with and without other findings such as skeletal myopathy, non-compaction and congenital heart defects (Lekanne Deprez, 2006; Tajsharghi, 2010; Berge, 2014; Wessels, 2015; van Velzen, 2017). Based on the available evidence, this alteration is classified as pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
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Pathogenic
(Jan 01, 2016)
C
Contributing to aggregate classification
|
criteria provided, single submitter
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Hypertrophic cardiomyopathy 4 |
Center for Medical Genetics Ghent, University of Ghent
Accession: SCV000299253.1
First in ClinVar: Sep 09, 2016 Last updated: Sep 09, 2016 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(Oct 08, 2014)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hypertrophic cardiomyopathy 4 |
Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743547.1 First in ClinVar: Apr 19, 2018 Last updated: Apr 19, 2018 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
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Pathogenic
(Sep 21, 2015)
C
Contributing to aggregate classification
|
criteria provided, single submitter
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Hypertrophic cardiomyopathy 4 |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744834.1 First in ClinVar: Apr 19, 2018 Last updated: Apr 19, 2018 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(May 28, 2021)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Cardiomyopathy |
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV002042176.1
First in ClinVar: Dec 29, 2021 Last updated: Dec 29, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
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Pathogenic
(Oct 04, 2017)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hypertrophic cardiomyopathy |
Royal Brompton Clinical Genetics And Genomics Laboratory, NHS South East Genomic Laboratory Hub
Accession: SCV000845659.2
First in ClinVar: Nov 03, 2018 Last updated: Dec 11, 2022 |
Comment:
show
This variant has been reported in mutiple unrelated HCM patients in the literature (refs 1-6, below), and has also been shown to segregate with disease in multiple affected individuals in several unrelated families (Wessels et al (2015) Eur J Hum Genet 23(7)922-928). Several other clinical laboraties have also detected the variant in HCM patients referred for genetic testing (ClinVar variation ID: 37039). The variant has also been detected in control populations at a very low frequency which is compatible with the prevalence of disease (ExAC and gnomAD databases). In view of the evidence, this variant is pathogenic. - References - 1. Alders et al. (2003) Eur Heart J. 24(20):1848-53. 2. Van et al. (2004) J Am Coll Cardiol. 44(9):1903-10. 3. Christiaans et al. (2010) Neth Heart J. 18(5):248-54. 4. Millat et al. (2010) Eur J Med Genet. 53(5):261-7. 5. Yiu et al. (2012) PLoS One. 7(5):e36115. 6. Alfares et al. (2015) Genet Med.17(11):880-8. - Population Controls alleles / total (frequency): Exome Aggregation Consortium (ExAC) - 2/117632 (0.00001700), RBH healthy cohort - 0/2144 (0.0) (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 4
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Pathogenic
(Jun 03, 2022)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
GeneDx
Accession: SCV000208124.16
First in ClinVar: Feb 24, 2015 Last updated: Mar 04, 2023 |
Comment:
show
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies using cardiomyocytes derived from induced pluripotent stem cells demonstrated this variant activates the nonsense-mediated decay pathway and results in aberrant calcium signaling and dysregulation of a set of other cardiac genes (Seeger et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19666645, 23674513, 25335496, 26026863, 18761664, 22569109, 28214152, 30731207, 31006259, 31918855, 31513939, 30847666, 32480058, 22574137, 16679492, 25525159, 26936621, 15519027, 19858127, 27532257, 23396983, 24510615, 22857948, 24111713, 28794111, 28396031, 28005231, 23233322, 20624503, 21839045, 19356534, 19574547, 30165862, 28797094, 29447731, 30742251, 31323898, 33673806, 32665702, 33662488, 32746448, 20505798, 30586709) (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
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Pathogenic
(Jan 22, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hypertrophic cardiomyopathy
(Autosomal dominant inheritance)
|
All of Us Research Program, National Institutes of Health
Accession: SCV004836706.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
show
This variant changes 1 nucleotide in exon 27 of the MYBPC3 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Functional RNA studies using cardiac tissue derived from a heterozygous carrier individual have shown that this variant causes a significant reduction in MYBPC3 mRNA levels (PMID: 33757590). This variant has been observed in over 20 unrelated individuals affected with hypertrophic cardiomyopathy (PMID: 16679492, 20624503, 22857948, 23233322, 24111713, 25335496, 27532257, 31006259, 31513939, 33757590, 36252119, 36835444) and is considered to be a founder mutation in the Dutch population (PMID: 20505798, 28794111). This variant has been reported to cause lethal cardiomyopathy or severe neonatal hypertrophic cardiomyopathy in individuals who were homozygous or compound heterozygous with another pathogenic mutation (PMID: 16679492, 24111713, 25335496, 30742251, 36178741). It has also been reported in two individuals affected with left ventricular noncompaction who both carried an additional different pathogenic variant (PMID: 31918855, 37963751), and in one individual affected with atrioventricular block (PMID: 35470684). This variant has been identified in 3/247124 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of MYBPC3 function is a known mechanism of disease. Based on available evidence, this variant is classified as Pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Number of individuals with the variant: 2
Zygosity: 2 Single Heterozygotes
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Pathogenic
(Jun 02, 2022)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hypertrophic cardiomyopathy 4 |
MGZ Medical Genetics Center
Accession: SCV002580166.2
First in ClinVar: Oct 15, 2022 Last updated: Apr 13, 2025
Comment:
ACMG criteria applied: PVS1, PS3, PM2_SUP, PP1
|
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Dec 18, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Cardiomyopathy |
Color Diagnostics, LLC DBA Color Health
Accession: SCV001344272.4
First in ClinVar: Jun 22, 2020 Last updated: May 03, 2025 |
Comment:
show
This variant changes 1 nucleotide in exon 27 of the MYBPC3 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Functional RNA studies using cardiac tissue derived from a heterozygous carrier individual have shown that this variant causes a significant reduction in MYBPC3 mRNA levels (PMID: 33757590). This variant has been observed in over 20 unrelated individuals affected with hypertrophic cardiomyopathy (PMID: 16679492, 20624503, 22857948, 23233322, 24111713, 25335496, 27532257, 31006259, 31513939, 33757590, 36252119, 36835444) and is considered to be a founder mutation in the Dutch population (PMID: 20505798, 28794111). This variant has been reported to cause lethal cardiomyopathy or severe neonatal hypertrophic cardiomyopathy in individuals who were homozygous or compound heterozygous with another pathogenic mutation (PMID: 16679492, 24111713, 25335496, 30742251, 36178741). It has also been reported in two individuals affected with left ventricular noncompaction who both carried an additional different pathogenic variant (PMID: 31918855, 37963751), and in one individual affected with atrioventricular block (PMID: 35470684). This variant has been identified in 3/247124 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of MYBPC3 function is a known mechanism of disease. Based on available evidence, this variant is classified as Pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Platform type: NGS
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Pathogenic
(Jan 20, 2025)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hypertrophic cardiomyopathy 4 |
Clinical Genetics Laboratory, Region Ostergotland
Accession: SCV007095741.1
First in ClinVar: Nov 02, 2025 Last updated: Nov 02, 2025 |
Comment:
show
The following ACMG/AMP criteria were applied in classifying this variant:: PVS1, PS4, PS3 (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 1
Zygosity: 1 Single Heterozygote
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Pathogenic
(Jan 13, 2026)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hypertrophic cardiomyopathy |
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000546480.12
First in ClinVar: Apr 17, 2017 Last updated: Mar 07, 2026 |
Comment:
show
This sequence change creates a premature translational stop signal (p.Arg943*) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). This variant is present in population databases (rs387907267, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with hypertrophic cardiomyopathy (PMID: 19574547, 20505798, 20624503, 22574137, 22857948, 23233322, 24111713, 25335496). It is commonly reported in individuals of Dutch ancestry (PMID: 19574547, 20505798, 20624503, 22574137, 22857948, 23233322, 24111713, 25335496). ClinVar contains an entry for this variant (Variation ID: 37039). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
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Pathogenic
(Feb 03, 2026)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
Dasa
Accession: SCV007599092.1
First in ClinVar: May 30, 2026 Last updated: May 30, 2026 |
Comment:
show
NM_000256.3(MYBPC3):c.2827C>T (p.Arg943*) introduces a premature termination codon predicted to result in loss of normal protein function. Loss-of-function is an established mechanism of disease for this gene. This variant has been observed in affected individuals with related phenotype in a genotype context consistent with recessive disease (PMID: 33049255; PMID: 16679492; PMID: 20624503; PMID: 22857948; PMID: 23233322). This variant has been recurrently observed in individuals with related phenotype (PMID: 33049255; PMID: 16679492; PMID: 20624503; PMID: 22857948; PMID: 23233322). The variant is present at low frequency in population datasets. Based on the available data, this variant is classified as pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
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Pathogenic
(Aug 28, 2025)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hypertrophic cardiomyopathy 4 |
3billion
Accession: SCV002521399.5
First in ClinVar: Jun 03, 2022 Last updated: Jun 20, 2026 |
Comment:
show
The variant is observed at an extremely low frequency in the gnomAD v4.1.0 dataset (total allele frequency: 0.001%). Predicted Consequence/Location: Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000037039 /PMID: 14563344 /3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Platform type: exome sequencing
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Pathogenic
(Apr 27, 2017)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000280245.3
First in ClinVar: May 29, 2016 Last updated: Aug 04, 2026 |
Observation: 1
Collection method: provider interpretation
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: provider interpretation
Allele origin: germline
Affected status: unknown
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Pathogenic
(Oct 31, 2018)
C
Contributing to aggregate classification
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criteria provided, single submitter
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Hypertrophic cardiomyopathy |
Center for Human Genetics, University of Leuven
Accession: SCV000886766.1
First in ClinVar: May 02, 2019 Last updated: May 02, 2019 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(Sep 13, 2018)
C
Contributing to aggregate classification
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criteria provided, single submitter
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not provided |
Blueprint Genetics
Accession: SCV000927931.1
First in ClinVar: Jul 24, 2019 Last updated: Jul 24, 2019
Comment:
Patient analyzed with Hypertrophic Cardiomyopathy (HCM) Panel
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Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(Aug 01, 2010)
N
Not contributing to aggregate classification
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no assertion criteria provided
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CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 4 |
OMIM
Accession: SCV000053360.3
First in ClinVar: Apr 04, 2013 Last updated: Aug 07, 2021 |
Observation: 1
Collection method: literature only
Allele origin: germline
Affected status: not provided
Observation 1
Collection method: literature only
Allele origin: germline
Affected status: not provided
Comment on evidence:
In a female infant with fatal cardiomyopathy (CMH4; 115197) who also had evidence of skeletal myopathy, Tajsharghi et al. (2010) identified homozygosity for a 2827C-T … (more)
In a female infant with fatal cardiomyopathy (CMH4; 115197) who also had evidence of skeletal myopathy, Tajsharghi et al. (2010) identified homozygosity for a 2827C-T transition, resulting in an arg943-to-ter (R943X) substitution in the MYBPC3 gene. Skeletal muscle biopsy at 2 months of age showed pronounced myopathic changes with numerous small fibers, which all expressed slow/beta-cardiac myosin heavy chain protein (MYH7; 160760). Electron microscopy revealed disorganization of the sarcomeres and partial depletion of thick filaments in the small fibers; immunohistochemical staining showed the presence of cardiac MYBPC in the small abnormal fibers. RT-PCR and sequencing demonstrated the mutation in transcripts of skeletal muscle. Tajsharghi et al. (2010) noted that cardiac MYBPC is not normally expressed in skeletal muscle, and stated that the reason for the ectopic expression of cardiac MYBPC remained unknown. The R943X mutation had previously been identified in compound heterozygosity with other truncating MYBPC3 mutations in 2 unrelated Dutch infants with fatal hypertrophic cardiomyopathy (Lekanne Deprez et al., 2006); skeletal myopathy was not mentioned in that report. (less)
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Pathogenic
(-)
N
Not contributing to aggregate classification
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no assertion criteria provided
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not provided |
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808627.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(-)
N
Not contributing to aggregate classification
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no assertion criteria provided
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not provided |
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV002035736.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(-)
N
Not contributing to aggregate classification
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no assertion criteria provided
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hypertrophic cardiomyopathy |
Zaffran Lab, Genetics of Cardiac Diseases Laboratory, Marseille Medical Genetics
Accession: SCV005374565.1
First in ClinVar: Oct 20, 2024 Last updated: Oct 20, 2024 |
Observation: 1
Collection method: research
Allele origin: unknown
Affected status: yes
Observation 1
Collection method: research
Allele origin: unknown
Affected status: yes
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Pathogenic
(-)
N
Not contributing to aggregate classification
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no assertion criteria provided
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not provided |
Clinical Genetics, Academic Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001919644.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(-)
N
Not contributing to aggregate classification
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no assertion criteria provided
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Hypertrophic cardiomyopathy 4 |
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733034.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(-)
N
Not contributing to aggregate classification
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no assertion criteria provided
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not provided |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Study: VKGL Data-share Consensus
Accession: SCV001955474.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Citation text
Lekanne Deprez, R. H., Muurling-Vlietman, J. J., Hruda, J., Baars, M. J. H., Wijnaendts, L. C. D., Stolte-Dijkstra, I., Alders, M., van Hagen, J. M. Two cases of severe neonatal hypertrophic cardiomyopathy caused by compound heterozygous mutations in the MYBPC3 gene. (Letter) J. Med. Genet. 43: 829-832, 2006.
Comment:
Variant summary: MYBPC3 c.2827C>T (p.Arg943X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 247124 control chromosomes (gnomAD). c.2827C>T has been reported in the literature in multiple individuals affected with Hypertrophic Cardiomyopathy (e.g. Van Driest_2004, Deprez_2006, Michels_2007, Berge_2013). These data indicate that the variant is very likely to be associated with disease. 15 clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
The p.Arg943X variant in MYBPC3 has been reported in >25 individuals with hypertrophic cardiomyopathy (HCM) and segregated with disease in 4 affected relatives in 4 families (Alders 2003 PMID: 14563344, Lekanne Deprez 2006 PMID: 16679492, Foksteun 2008 PMID: 18409188, Morita 2008 PMID: 18403758, Michels 2009 PMID: 19356534, Van Driest 2004 PMID: 15519027, Tajsharghi 2010 PMID: 19858127, Yiu 2012 PMID: 22574137, Wessels 2014 PMID: 25335496, LMM unpublished data). Several of these individuals carried an additional clinically significant variant and presented with early onset disease. This variant has been reported by other clinical laboratories in ClinVar (Variation ID 37039) and has also been identified in 0.006% (2/30444) of South Asian chromosomes by gnomAD (https://gnomad.broadinstitute.org/). This nonsense variant leads to a premature termination codon at position 943, which is predicted to lead to a truncated or absent protein. Loss of function of the MYBPC3 gene is an established disease mechanism in autosomal dominant HCM. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HCM. ACMG/AMP criteria applied: PVS1, PS4, PP1, PM2_supporting.
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with hypertrophic cardiomyopathy 4 (HCM; MIM#115197). (I) 0108 - This gene is associated with both recessive and dominant disease. Dominant inheritance is frequently reported in adult onset conditions, however recessive inheritance results in a more severe early onset phenotype (OMIM). (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 32841044). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (4 heterozygotes, 0 homozygotes). (SP) 0701 - Other null variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. There are at least ten pathogenic NMD-predicted variants that have been reported (DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant is a Dutch founder variant and has been classified as pathogenic by multiple diagnostic laboratories. This variant has also been reported to be compound heterozygous or homozygous in individuals with severe early-onset disease (ClinVar, PMID: 25335496). (SP) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) heterozygous for this variant demonstrated aberrant calcium signalling and prolonged relaxation kinetics compared to WT cells, with homozygous iPSC-CMs demonstrating more severe impairment (PMID: 30586709). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Comment:
The c.2827C>T (p.R943*) alteration, located in exon 27 (coding exon 27) of the MYBPC3 gene, consists of a C to T substitution at nucleotide position 2827. This changes the amino acid from a arginine (R) to a stop codon at amino acid position 943. This variant is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of 0.001% (3/247124) total alleles studied. The highest observed frequency was 0.007% (2/30444) of South Asian alleles. This variant was reported in individual(s) with features consistent with hypertrophic cardiomyopathy, and has been reported as a Dutch founder mutation (Van Driest, 2004; Michels, 2007; Michels, 2009; Christiaans, 2010; Brito, 2012; Hathaway, 2021). This variant has been reported as occurring in the homozygous state and also with other alterations in patients with severe, early onset disease with and without other findings such as skeletal myopathy, non-compaction and congenital heart defects (Lekanne Deprez, 2006; Tajsharghi, 2010; Berge, 2014; Wessels, 2015; van Velzen, 2017). Based on the available evidence, this alteration is classified as pathogenic.
Comment:
This variant has been reported in mutiple unrelated HCM patients in the literature (refs 1-6, below), and has also been shown to segregate with disease in multiple affected individuals in several unrelated families (Wessels et al (2015) Eur J Hum Genet 23(7)922-928). Several other clinical laboraties have also detected the variant in HCM patients referred for genetic testing (ClinVar variation ID: 37039). The variant has also been detected in control populations at a very low frequency which is compatible with the prevalence of disease (ExAC and gnomAD databases). In view of the evidence, this variant is pathogenic. - References - 1. Alders et al. (2003) Eur Heart J. 24(20):1848-53. 2. Van et al. (2004) J Am Coll Cardiol. 44(9):1903-10. 3. Christiaans et al. (2010) Neth Heart J. 18(5):248-54. 4. Millat et al. (2010) Eur J Med Genet. 53(5):261-7. 5. Yiu et al. (2012) PLoS One. 7(5):e36115. 6. Alfares et al. (2015) Genet Med.17(11):880-8. - Population Controls alleles / total (frequency): Exome Aggregation Consortium (ExAC) - 2/117632 (0.00001700), RBH healthy cohort - 0/2144 (0.0)
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies using cardiomyocytes derived from induced pluripotent stem cells demonstrated this variant activates the nonsense-mediated decay pathway and results in aberrant calcium signaling and dysregulation of a set of other cardiac genes (Seeger et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19666645, 23674513, 25335496, 26026863, 18761664, 22569109, 28214152, 30731207, 31006259, 31918855, 31513939, 30847666, 32480058, 22574137, 16679492, 25525159, 26936621, 15519027, 19858127, 27532257, 23396983, 24510615, 22857948, 24111713, 28794111, 28396031, 28005231, 23233322, 20624503, 21839045, 19356534, 19574547, 30165862, 28797094, 29447731, 30742251, 31323898, 33673806, 32665702, 33662488, 32746448, 20505798, 30586709)
Comment:
This variant changes 1 nucleotide in exon 27 of the MYBPC3 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Functional RNA studies using cardiac tissue derived from a heterozygous carrier individual have shown that this variant causes a significant reduction in MYBPC3 mRNA levels (PMID: 33757590). This variant has been observed in over 20 unrelated individuals affected with hypertrophic cardiomyopathy (PMID: 16679492, 20624503, 22857948, 23233322, 24111713, 25335496, 27532257, 31006259, 31513939, 33757590, 36252119, 36835444) and is considered to be a founder mutation in the Dutch population (PMID: 20505798, 28794111). This variant has been reported to cause lethal cardiomyopathy or severe neonatal hypertrophic cardiomyopathy in individuals who were homozygous or compound heterozygous with another pathogenic mutation (PMID: 16679492, 24111713, 25335496, 30742251, 36178741). It has also been reported in two individuals affected with left ventricular noncompaction who both carried an additional different pathogenic variant (PMID: 31918855, 37963751), and in one individual affected with atrioventricular block (PMID: 35470684). This variant has been identified in 3/247124 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of MYBPC3 function is a known mechanism of disease. Based on available evidence, this variant is classified as Pathogenic.
Comment:
This variant changes 1 nucleotide in exon 27 of the MYBPC3 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Functional RNA studies using cardiac tissue derived from a heterozygous carrier individual have shown that this variant causes a significant reduction in MYBPC3 mRNA levels (PMID: 33757590). This variant has been observed in over 20 unrelated individuals affected with hypertrophic cardiomyopathy (PMID: 16679492, 20624503, 22857948, 23233322, 24111713, 25335496, 27532257, 31006259, 31513939, 33757590, 36252119, 36835444) and is considered to be a founder mutation in the Dutch population (PMID: 20505798, 28794111). This variant has been reported to cause lethal cardiomyopathy or severe neonatal hypertrophic cardiomyopathy in individuals who were homozygous or compound heterozygous with another pathogenic mutation (PMID: 16679492, 24111713, 25335496, 30742251, 36178741). It has also been reported in two individuals affected with left ventricular noncompaction who both carried an additional different pathogenic variant (PMID: 31918855, 37963751), and in one individual affected with atrioventricular block (PMID: 35470684). This variant has been identified in 3/247124 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of MYBPC3 function is a known mechanism of disease. Based on available evidence, this variant is classified as Pathogenic.
Comment:
The following ACMG/AMP criteria were applied in classifying this variant:: PVS1, PS4, PS3
Comment:
This sequence change creates a premature translational stop signal (p.Arg943*) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). This variant is present in population databases (rs387907267, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with hypertrophic cardiomyopathy (PMID: 19574547, 20505798, 20624503, 22574137, 22857948, 23233322, 24111713, 25335496). It is commonly reported in individuals of Dutch ancestry (PMID: 19574547, 20505798, 20624503, 22574137, 22857948, 23233322, 24111713, 25335496). ClinVar contains an entry for this variant (Variation ID: 37039). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Comment:
NM_000256.3(MYBPC3):c.2827C>T (p.Arg943*) introduces a premature termination codon predicted to result in loss of normal protein function. Loss-of-function is an established mechanism of disease for this gene. This variant has been observed in affected individuals with related phenotype in a genotype context consistent with recessive disease (PMID: 33049255; PMID: 16679492; PMID: 20624503; PMID: 22857948; PMID: 23233322). This variant has been recurrently observed in individuals with related phenotype (PMID: 33049255; PMID: 16679492; PMID: 20624503; PMID: 22857948; PMID: 23233322). The variant is present at low frequency in population datasets. Based on the available data, this variant is classified as pathogenic.
Comment:
The variant is observed at an extremely low frequency in the gnomAD v4.1.0 dataset (total allele frequency: 0.001%). Predicted Consequence/Location: Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000037039 /PMID: 14563344 /3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| [Clinical phenotype and genetic analysis of patients with left ventricular noncompaction caused by the biallelic mutation of MYBPC3 and MYH7]. | Zhang YH | Zhonghua xin xue guan bing za zhi | 2023 | PMID: 37963751 |
| Untargeted Metabolomics Identifies Potential Hypertrophic Cardiomyopathy Biomarkers in Carriers of MYBPC3 Founder Variants. | Jansen M | International journal of molecular sciences | 2023 | PMID: 36835444 |
| Genetic Basis of Childhood Cardiomyopathy. | Bagnall RD | Circulation. Genomic and precision medicine | 2022 | PMID: 36252119 |
| Genetic Evaluation of A Nation-Wide Dutch Pediatric DCM Cohort: The Use of Genetic Testing in Risk Stratification. | van der Meulen MH | Circulation. Genomic and precision medicine | 2022 | PMID: 36178741 |
| Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause. | Resdal Dyssekilde J | Journal of the American Heart Association | 2022 | PMID: 35470684 |
| Multi-omics integration identifies key upstream regulators of pathomechanisms in hypertrophic cardiomyopathy due to truncating MYBPC3 mutations. | Pei J | Clinical epigenetics | 2021 | PMID: 33757590 |
| Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients. | Hathaway J | BMC cardiovascular disorders | 2021 | PMID: 33673806 |
| Targeting the population for gene therapy with MYBPC3. | Carrier L | Journal of molecular and cellular cardiology | 2021 | PMID: 33049255 |
| Spatial and Functional Distribution of MYBPC3 Pathogenic Variants and Clinical Outcomes in Patients With Hypertrophic Cardiomyopathy. | Helms AS | Circulation. Genomic and precision medicine | 2020 | PMID: 32841044 |
| Multiple genetic variants in adolescent patients with left ventricular noncompaction cardiomyopathy. | Liu S | International journal of cardiology | 2020 | PMID: 31918855 |
| Clinical and ECG variables to predict the outcome of genetic testing in hypertrophic cardiomyopathy. | Robyns T | European journal of medical genetics | 2020 | PMID: 31513939 |
| Yield of Clinical Screening for Hypertrophic Cardiomyopathy in Child First-Degree Relatives. | Norrish G | Circulation | 2019 | PMID: 31006259 |
| Fatal neonatal hypertrophic cardiomyopathy caused by compound heterozygous truncating MYBPC3 mutation. | Alsters S | Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation | 2019 | PMID: 30742251 |
| A Premature Termination Codon Mutation in MYBPC3 Causes Hypertrophic Cardiomyopathy via Chronic Activation of Nonsense-Mediated Decay. | Seeger T | Circulation | 2019 | PMID: 30586709 |
| Clinical Characteristics and Long-Term Outcome of Hypertrophic Cardiomyopathy in Individuals With a MYBPC3 (Myosin-Binding Protein C) Founder Mutation. | van Velzen HG | Circulation. Cardiovascular genetics | 2017 | PMID: 28794111 |
| Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. | Walsh R | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 27532257 |
| Compound heterozygous or homozygous truncating MYBPC3 mutations cause lethal cardiomyopathy with features of noncompaction and septal defects. | Wessels MW | European journal of human genetics : EJHG | 2015 | PMID: 25335496 |
| Genetics of hypertrophic cardiomyopathy in Norway. | Berge KE | Clinical genetics | 2014 | PMID: 24111713 |
| Early results of sarcomeric gene screening from the Egyptian National BA-HCM Program. | Kassem HSh | Journal of cardiovascular translational research | 2013 | PMID: 23233322 |
| Sarcomeric hypertrophic cardiomyopathy: genetic profile in a Portuguese population. | Brito D | Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology | 2012 | PMID: 22857948 |
| Myocardial structural alteration and systolic dysfunction in preclinical hypertrophic cardiomyopathy mutation carriers. | Yiu KH | PloS one | 2012 | PMID: 22574137 |
| Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy. | Millat G | European journal of medical genetics | 2010 | PMID: 20624503 |
| Founder mutations in hypertrophic cardiomyopathy patients in the Netherlands. | Christiaans I | Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation | 2010 | PMID: 20505798 |
| Unexpected myopathy associated with a mutation in MYBPC3 and misplacement of the cardiac myosin binding protein C. | Tajsharghi H | Journal of medical genetics | 2010 | PMID: 19858127 |
| Evidence from human myectomy samples that MYBPC3 mutations cause hypertrophic cardiomyopathy through haploinsufficiency. | Marston S | Circulation research | 2009 | PMID: 19574547 |
| Diastolic abnormalities as the first feature of hypertrophic cardiomyopathy in Dutch myosin-binding protein C founder mutations. | Michels M | JACC. Cardiovascular imaging | 2009 | PMID: 19356534 |
| A DNA resequencing array for pathogenic mutation detection in hypertrophic cardiomyopathy. | Fokstuen S | Human mutation | 2008 | PMID: 18409188 |
| Shared genetic causes of cardiac hypertrophy in children and adults. | Morita H | The New England journal of medicine | 2008 | PMID: 18403758 |
| Familial screening and genetic counselling in hypertrophic cardiomyopathy: the Rotterdam experience. | Michels M | Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation | 2007 | PMID: 17612681 |
| Two cases of severe neonatal hypertrophic cardiomyopathy caused by compound heterozygous mutations in the MYBPC3 gene. | Lekanne Deprez RH | Journal of medical genetics | 2006 | PMID: 16679492 |
| Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy. | Van Driest SL | Journal of the American College of Cardiology | 2004 | PMID: 15519027 |
| The 2373insG mutation in the MYBPC3 gene is a founder mutation, which accounts for nearly one-fourth of the HCM cases in the Netherlands. | Alders M | European heart journal | 2003 | PMID: 14563344 |
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Text-mined citations for rs387907267 ...
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Record last updated Aug 04, 2026
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.