VCV000042702.16 - ClinVar

NM_000256.3(MYBPC3):c.3297dup (p.Tyr1100fs)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic/Likely pathogenic
Pathogenic (3); Likely pathogenic (1)

4 out of 4 submissions contributed to this classification

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000256.3(MYBPC3):c.3297dup (p.Tyr1100fs)

Variation ID: 42702 Accession: VCV000042702.16

Type and length

Duplication, 1 bp

Location

Cytogenetic: 11p11.2 11: 47333226-47333227 (GRCh38) [ NCBI UCSC ] 11: 47354777-47354778 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Feb 6, 2015	Aug 4, 2026	Oct 7, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000256.3:c.3297dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000247.2:p.Tyr1100fs
NM_000256.3:c.3297dupG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NC_000011.10:g.47333231dup
NC_000011.9:g.47354782dup
NG_007667.1:g.24476dup
LRG_386:g.24476dup
LRG_386t1:c.3297dup	LRG_386p1:p.Tyr1100fs

... more HGVS ... less HGVS

Protein change

Y1100fs

Other names

p.Tyr1100ValfsX49

Canonical SPDI

NC_000011.10:47333226:CCCCC:CCCCCC

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA013831 dbSNP: rs397516014 VarSome

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
Gene	OMIM	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.
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.
not provided	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Nov 30, 2018	RCV000223806.12
Hypertrophic cardiomyopathy	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Oct 7, 2025	RCV000844680.19

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.
Pathogenic (Oct 07, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Hypertrophic cardiomyopathy	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001201680.7 First in ClinVar: Apr 15, 2020 Last updated: Feb 15, 2026	Publications: PubMed (2) PubMed: 19574547‚ 27532257 Comment: show This sequence change creates a premature translational stop signal (p.Tyr1100Valfs*49) 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 (rs397516014, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 42702). 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

Pathogenic (Nov 30, 2018) C Contributing to aggregate classification	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	not provided	Blueprint Genetics Accession: SCV000928090.2 First in ClinVar: Jul 31, 2019 Last updated: Apr 15, 2023 Comment: Patient analyzed with Hypertrophic Cardiomyopathy (HCM) Panel	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Feb 13, 2012) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	Hypertrophic cardiomyopathy	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000059226.5 First in ClinVar: May 03, 2013 Last updated: May 29, 2016	Comment: show The Tyr1100fs variant (MYBPC3) has not been reported in the literature but has b een identified in one individual with HCM (this individual's father) by our labo ratory. This frameshift variant is predicted to alter the protein?s amino acid sequence beginning at position 1100 and lead to a premature termination codon 49 amino acids downstream. This alteration is then predicted to lead to a truncate d or absent protein. Heterozygous loss of function of the MYBPC3 gene is an esta blished disease mechanism in HCM, which makes it highly likely that this variant is pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: not provided more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: not provided Number of individuals with the variant: 4

Likely pathogenic (Aug 29, 2013) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided	Stanford Center for Inherited Cardiovascular Disease, Stanford University Accession: SCV000280259.2 First in ClinVar: Jun 03, 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

Comment:

This sequence change creates a premature translational stop signal (p.Tyr1100Valfs*49) 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 (rs397516014, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 42702). For these reasons, this variant has been classified as Pathogenic.

Comment:

The Tyr1100fs variant (MYBPC3) has not been reported in the literature but has b een identified in one individual with HCM (this individual's father) by our labo ratory. This frameshift variant is predicted to alter the protein?s amino acid sequence beginning at position 1100 and lead to a premature termination codon 49 amino acids downstream. This alteration is then predicted to lead to a truncate d or absent protein. Heterozygous loss of function of the MYBPC3 gene is an esta blished disease mechanism in HCM, which makes it highly likely that this variant is pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
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
Evidence from human myectomy samples that MYBPC3 mutations cause hypertrophic cardiomyopathy through haploinsufficiency.	Marston S	Circulation research	2009	PMID: 19574547

Text-mined citations for rs397516014 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 04, 2026