VCV000177870.5 - ClinVar

NM_000256.3(MYBPC3):c.2604_2605delinsA (p.Ser871fs)

Germline

Classification

no assertion criteria provided. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (2)

2 out of 2 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.2604_2605delinsA (p.Ser871fs)

Variation ID: 177870 Accession: VCV000177870.5

Type and length

Indel, 2 bp

Location

Cytogenetic: 11p11.2 11: 47336009-47336010 (GRCh38) [ NCBI UCSC ] 11: 47357560-47357561 (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	May 29, 2016	Aug 23, 2020	Dec 6, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NM_000256.3:c.2604_2605delTCinsA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000256.3:c.2604_2605delinsA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000247.2:p.Ser871fs	frameshift
NC_000011.10:g.47336009_47336010delinsT
NC_000011.9:g.47357560_47357561delinsT
NG_007667.1:g.21693_21694delinsA
LRG_386:g.21693_21694delinsA
LRG_386t1:c.2604_2605delinsA	LRG_386p1:p.Ser871fs

... more HGVS ... less HGVS

Protein change

S871fs

Other names

Canonical SPDI

NC_000011.10:47336008:GA:T

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: CA012683 dbSNP: rs727504371 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	4728	4750

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.
Hypertrophic cardiomyopathy	Pathogenic (2)	no assertion criteria provided	Dec 6, 2019	RCV000154510.6

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 (Mar 05, 2013) C Contributing to aggregate classification	no assertion criteria provided	Hypertrophic cardiomyopathy (Autosomal dominant inheritance)	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000204181.3 First in ClinVar: Jan 31, 2015 Last updated: May 29, 2016	Comment: show proposed classification - variant undergoing re-assessment, contact laboratory (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

Pathogenic (Dec 06, 2019) C Contributing to aggregate classification	no assertion criteria provided	Hypertrophic cardiomyopathy (Autosomal dominant inheritance)	Agnes Ginges Centre for Molecular Cardiology, Centenary Institute Accession: SCV001430843.1 First in ClinVar: Aug 23, 2020 Last updated: Aug 23, 2020	Publications: PubMed (6) PubMed: 19219553‚ 19574547‚ 23396983‚ 27532257‚ 27600940‚ 28408708 Comment: show The MYBPC3 Ser871Alafs8 variant has been seen previously in >10 HCM probands (Lopes JR, et al., 2013; Jacques A, et al., 2008; Walsh et al., 2017) and is absent in the Genome Aggregation Database (http://gnomad.broadinstitute.org/). We identified this variant in a HCM proband with no family history of disease or sudden cardiac death (Ingles et al, 2017). Based on the adapted ACMG guidelines (Kelly MA, et al., 2018) this variant results in loss of function of MYBPC3 (PVS1), has been reported in more than 10 unrelated HCM probands (PS4) and is rare in the general population (PM2), therefore we classify MYBPC3 Ser871Alafs8 as a "pathogenic" variant. (less) Observation: 1 Collection method: research Allele origin: germline Affected status: yes Observation 1 Collection method: research Allele origin: germline Affected status: yes

Comment:

The MYBPC3 Ser871Alafs*8 variant has been seen previously in >10 HCM probands (Lopes JR, et al., 2013; Jacques A, et al., 2008; Walsh et al., 2017) and is absent in the Genome Aggregation Database (http://gnomad.broadinstitute.org/). We identified this variant in a HCM proband with no family history of disease or sudden cardiac death (Ingles et al, 2017). Based on the adapted ACMG guidelines (Kelly MA, et al., 2018) this variant results in loss of function of MYBPC3 (PVS1), has been reported in more than 10 unrelated HCM probands (PS4) and is rare in the general population (PM2), therefore we classify MYBPC3 Ser871Alafs*8 as a "pathogenic" variant.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Nonfamilial Hypertrophic Cardiomyopathy: Prevalence, Natural History, and Clinical Implications.	Ingles J	Circulation. Cardiovascular genetics	2017	PMID: 28408708
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
Targeted next-generation sequencing helps to decipher the genetic and phenotypic heterogeneity of hypertrophic cardiomyopathy.	Cecconi M	International journal of molecular medicine	2016	PMID: 27600940
Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing.	Lopes LR	Journal of medical genetics	2013	PMID: 23396983
Evidence from human myectomy samples that MYBPC3 mutations cause hypertrophic cardiomyopathy through haploinsufficiency.	Marston S	Circulation research	2009	PMID: 19574547
From genotype to phenotype: a longitudinal study of a patient with hypertrophic cardiomyopathy due to a mutation in the MYBPC3 gene.	Jacques A	Journal of muscle research and cell motility	2008	PMID: 19219553

Text-mined citations for rs727504371 ...

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 Dec 20, 2025