VCV000449310.18 - ClinVar

NC_000011.10:g.47351385_47351387del

Germline

Classification

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

Uncertain significance
Uncertain significance (5)

5 out of 5 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

NC_000011.10:g.47351385_47351387del

Variation ID: 449310 Accession: VCV000449310.18

Type and length

Deletion, 3 bp

Location

Cytogenetic: 11p11.2 11: 47351383-47351385 (GRCh38) [ NCBI UCSC ] 11: 47372934-47372936 (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	Dec 19, 2017	Jul 27, 2026	Nov 1, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000256.3:c.146_148delTCA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		inframe deletion
NC_000011.10:g.47351385_47351387del
NC_000011.9:g.47372936_47372938del
NG_007667.1:g.6318_6320del
LRG_386:g.6318_6320del
LRG_386t1:c.146_148del	LRG_386p1:p.Ile49del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000011.10:47351382:TGATG:TG

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: CA045293 dbSNP: rs781207661 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	4724	4746

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	Uncertain significance (3)	criteria provided, multiple submitters, no conflicts	Nov 1, 2025	RCV000788319.11
Hypertrophic cardiomyopathy	Uncertain significance (1)	criteria provided, single submitter	Jun 16, 2025	RCV001297213.7
Cardiomyopathy	Uncertain significance (1)	criteria provided, single submitter	Apr 26, 2024	RCV003532153.2

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.
Uncertain significance (Aug 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	not provided	Blueprint Genetics Accession: SCV000927382.1 First in ClinVar: Jul 25, 2019 Last updated: Jul 25, 2019 Comment: Patient analyzed with Hypertrophic Cardiomyopathy (HCM) Panel	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Oct 30, 2023) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000617257.4 First in ClinVar: Dec 19, 2017 Last updated: Sep 16, 2024	Comment: show Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; Identified in patients with cardiomyopathy referred for genetic testing at GeneDx and in published literature (PMID: 29169752, 24111713, 35653365, 27532257); This variant is associated with the following publications: (PMID: 27532257, 29169752, 24111713, 35653365) (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

Uncertain significance (Apr 26, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cardiomyopathy	Color Diagnostics, LLC DBA Color Health Accession: SCV004359289.2 First in ClinVar: Feb 14, 2024 Last updated: May 03, 2025	Publications: PubMed (4) PubMed: 24111713‚ 27532257‚ 28971120‚ 33495596 Comment: show This variant causes an in-frame deletion of one amino acid at exon 2 of the MYBPC3 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least 4 individuals affected with hypertrophic cardiomyopathy (PMID: 24111713, 27532257, 28971120, 33495596). This variant has been identified in 3/239780 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Platform type: NGS

Uncertain significance (Jun 16, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Hypertrophic cardiomyopathy	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001486199.6 First in ClinVar: Mar 07, 2021 Last updated: Feb 15, 2026	Publications: PubMed (6) PubMed: 24111713‚ 26090888‚ 27532257‚ 33495596‚ 35653365‚ 37652022 Comment: show This variant, c.146_148del, results in the deletion of 1 amino acid(s) of the MYBPC3 protein (p.Ile49del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs781207661, gnomAD 0.003%). This variant has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 24111713, 27532257, 33495596, 35653365, 37652022; internal data). ClinVar contains an entry for this variant (Variation ID: 449310). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the MYBPC3 protein in which other variant(s) (p.Ile49Ser) have been observed in individuals with MYBPC3-related conditions (PMID: 26090888). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (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

Uncertain significance (Nov 01, 2025) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV007117406.5 First in ClinVar: Dec 14, 2025 Last updated: Jul 27, 2026	Comment: show MYBPC3: PS4:Moderate, PM2:Supporting, PM4:Supporting (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Comment:

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; Identified in patients with cardiomyopathy referred for genetic testing at GeneDx and in published literature (PMID: 29169752, 24111713, 35653365, 27532257); This variant is associated with the following publications: (PMID: 27532257, 29169752, 24111713, 35653365)

Comment:

This variant causes an in-frame deletion of one amino acid at exon 2 of the MYBPC3 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least 4 individuals affected with hypertrophic cardiomyopathy (PMID: 24111713, 27532257, 28971120, 33495596). This variant has been identified in 3/239780 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

Comment:

This variant, c.146_148del, results in the deletion of 1 amino acid(s) of the MYBPC3 protein (p.Ile49del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs781207661, gnomAD 0.003%). This variant has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 24111713, 27532257, 33495596, 35653365, 37652022; internal data). ClinVar contains an entry for this variant (Variation ID: 449310). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the MYBPC3 protein in which other variant(s) (p.Ile49Ser) have been observed in individuals with MYBPC3-related conditions (PMID: 26090888). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
The penetrance of rare variants in cardiomyopathy-associated genes: A cross-sectional approach to estimating penetrance for secondary findings.	McGurk KA	American journal of human genetics	2023	PMID: 37652022
Molecular genetics in 4408 cardiomyopathy probands and 3008 relatives in Norway: 17 years of genetic testing in a national laboratory.	Stava TT	European journal of preventive cardiology	2022	PMID: 35653365
Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect.	Tadros R	Nature genetics	2021	PMID: 33495596
Data on exercise and cardiac imaging in a patient cohort with hypertrophic cardiomyopathy.	Dejgaard LA	Data in brief	2017	PMID: 28971120
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
Screening Mutations of MYBPC3 in 114 Unrelated Patients with Hypertrophic Cardiomyopathy by Targeted Capture and Next-generation Sequencing.	Liu X	Scientific reports	2015	PMID: 26090888
Genetics of hypertrophic cardiomyopathy in Norway.	Berge KE	Clinical genetics	2014	PMID: 24111713

Text-mined citations for rs781207661 ...

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 Jul 27, 2026