VCV000181083.15 - ClinVar

NC_000011.10:g.47336009del

Germline

Classification

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

Pathogenic/Likely pathogenic
Pathogenic (3); Likely pathogenic (2)

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.47336009del

Variation ID: 181083 Accession: VCV000181083.15

Type and length

Deletion, 1 bp

Location

Cytogenetic: 11p11.2 11: 47336004 (GRCh38) [ NCBI UCSC ] 11: 47357555 (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	Feb 15, 2026	Dec 31, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000256.3:c.2610delC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		frameshift
NC_000011.10:g.47336009del
NC_000011.9:g.47357560del
NG_007667.1:g.21699del
LRG_386:g.21699del
LRG_386t1:c.2610del	LRG_386p1:p.Ser871fs

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000011.10:47336003:GGGGGG:GGGGG

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: CA012712 dbSNP: rs397515979 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.
not provided	Pathogenic (1)	criteria provided, single submitter	May 21, 2020	RCV000158372.5
Hypertrophic cardiomyopathy	Pathogenic/Likely pathogenic (3)	criteria provided, multiple submitters, no conflicts	Dec 31, 2025	RCV000768474.12
Cardiomyopathy	Pathogenic (1)	criteria provided, single submitter	Mar 5, 2019	RCV001170202.2

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.
Pathogenic (Mar 05, 2019) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cardiomyopathy	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Accession: SCV001332754.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely Pathogenic (Oct 14, 2019) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hypertrophic cardiomyopathy	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV004847802.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024	Publications: PubMed (3) PubMed: 20031618‚ 27532257‚ 27600940 Comment: show The p.Ser871AlafsX8 variant in MYBPC3 has been reported in at least 6 individuals with hypertrophic cardiomyopathy (Kaski 2009, Walsh 2017, Cecconi 2016). It was also identified in 11/168356 chromosomes by gnomAD (https://gnomad.broadinstitute.org); however, average read depth at this location was low, so the reliability of this data is unclear. The variant has also been reported in ClinVar (Variation ID 181083). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 871 and leads to a premature termination codon 8 amino acids downstream. This alteration is then 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. (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 (Dec 31, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Hypertrophic cardiomyopathy	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001416209.7 First in ClinVar: Jul 16, 2020 Last updated: Feb 15, 2026	Publications: PubMed (4) PubMed: 19574547‚ 20031618‚ 27532257‚ 27600940 Comment: show This sequence change creates a premature translational stop signal (p.Ser871Alafs*8) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 20031618, 27532257, 27600940). This variant is also known as P870fs878X. ClinVar contains an entry for this variant (Variation ID: 181083). 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

Likely pathogenic (Oct 31, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hypertrophic cardiomyopathy	Center for Human Genetics, University of Leuven Accession: SCV000886762.1 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

Pathogenic (May 21, 2020) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000208307.13 First in ClinVar: Feb 24, 2015 Last updated: Apr 17, 2019	Comment: show Frameshift 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; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 20031618, 27532257, 25351510, 27600940, 31513939) (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

Comment:

The p.Ser871AlafsX8 variant in MYBPC3 has been reported in at least 6 individuals with hypertrophic cardiomyopathy (Kaski 2009, Walsh 2017, Cecconi 2016). It was also identified in 11/168356 chromosomes by gnomAD (https://gnomad.broadinstitute.org); however, average read depth at this location was low, so the reliability of this data is unclear. The variant has also been reported in ClinVar (Variation ID 181083). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 871 and leads to a premature termination codon 8 amino acids downstream. This alteration is then 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.

Comment:

This sequence change creates a premature translational stop signal (p.Ser871Alafs*8) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 20031618, 27532257, 27600940). This variant is also known as P870fs878X. ClinVar contains an entry for this variant (Variation ID: 181083). For these reasons, this variant has been classified as Pathogenic.

Comment:

Frameshift 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; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 20031618, 27532257, 25351510, 27600940, 31513939)

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
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
Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy.	Kaski JP	Circulation. Cardiovascular genetics	2009	PMID: 20031618
Evidence from human myectomy samples that MYBPC3 mutations cause hypertrophic cardiomyopathy through haploinsufficiency.	Marston S	Circulation research	2009	PMID: 19574547

Text-mined citations for rs397515979 ...

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 Feb 15, 2026