VCV000042786.52 - ClinVar

NM_000256.3(MYBPC3):c.706A>G (p.Ser236Gly)

Germline

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.

(23)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000256.3(MYBPC3):c.706A>G (p.Ser236Gly)

Variation ID: 42786 Accession: VCV000042786.52

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p11.2 11: 47348490 (GRCh38) [ NCBI UCSC ] 11: 47370041 (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	Sep 14, 2015	Sep 29, 2024	Feb 5, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000256.3:c.706A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000247.2:p.Ser236Gly	missense
NC_000011.10:g.47348490T>C
NC_000011.9:g.47370041T>C
NG_007667.1:g.9213A>G
LRG_386:g.9213A>G
LRG_386t1:c.706A>G	LRG_386p1:p.Ser236Gly
	Q14896:p.Ser236Gly

... more HGVS ... less HGVS

Protein change

S236G

Other names

p.S236G:AGC>GGC

Canonical SPDI

NC_000011.10:47348489:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

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.

0.06709 (C)

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

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.10344

Exome Aggregation Consortium (ExAC) 0.10789

1000 Genomes Project 30x 0.06683

1000 Genomes Project 0.06709

Trans-Omics for Precision Medicine (TOPMed) 0.08941

The Genome Aggregation Database (gnomAD) 0.09621

The Genome Aggregation Database (gnomAD), exomes 0.09643

Links

ClinGen: CA015725 UniProtKB: Q14896#VAR_020086 dbSNP: rs3729989 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	3959	3978

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 specified	Benign (6)	criteria provided, multiple submitters, no conflicts	Mar 12, 2013	RCV000035662.33
Hypertrophic cardiomyopathy	Benign (4)	criteria provided, multiple submitters, no conflicts	Feb 5, 2024	RCV000172761.26
Cardiovascular phenotype	Benign (1)	criteria provided, single submitter	Mar 11, 2015	RCV000252619.11
Left ventricular noncompaction 10	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Sep 5, 2021	RCV000289076.15
Hypertrophic cardiomyopathy 4	Benign/Likely benign (5)	criteria provided, multiple submitters, no conflicts	Sep 5, 2021	RCV000604115.16
not provided	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Nov 27, 2023	RCV000757503.27
Cardiomyopathy	Benign (1)	criteria provided, single submitter	Mar 19, 2018	RCV000776002.10

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.	More information 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.
Benign (Jun 24, 2013)	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013)) Method: research	Cardiomyopathy, hypertrophic Affected status: unknown Allele origin: unknown	Biesecker Lab/Clinical Genomics Section, National Institutes of Health Study: ClinSeq Accession: SCV000051566.2 First in ClinVar: Jun 08, 2015 Last updated: Sep 14, 2015 Comments (2): The study set was not selected for affection status in relation to any cancer. HGMD phenotype assertion is uncertain. Pathogenicity categories were based on literature … (more) The study set was not selected for affection status in relation to any cancer. HGMD phenotype assertion is uncertain. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less) Medical sequencing	Number of individuals with the variant: 115
Benign (Jul 12, 2011)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000170451.11 First in ClinVar: Jun 23, 2014 Last updated: Oct 02, 2016	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (Mar 12, 2013)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000110304.8 First in ClinVar: Jan 17, 2014 Last updated: Sep 22, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MYBPC3 Number of individuals with the variant: 1 Sex: mixed
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hypertrophic cardiomyopathy Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001000287.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024
Benign (Mar 11, 2015)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000317846.7 First in ClinVar: Oct 02, 2016 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Benign (Sep 21, 2015)	criteria provided, single submitter (ACGS Guidelines, 2013) Method: clinical testing	Hypertrophic cardiomyopathy 4 Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Study: VKGL Data-share Consensus Accession: SCV000744869.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Benign (Mar 19, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cardiomyopathy Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000910535.1 First in ClinVar: May 20, 2019 Last updated: May 20, 2019
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: yes Allele origin: germline	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute Accession: SCV000987330.1 First in ClinVar: Sep 09, 2019 Last updated: Sep 09, 2019
Likely benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Left ventricular noncompaction 10 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000372394.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Likely benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Hypertrophic cardiomyopathy 4 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000372393.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Benign (Nov 27, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000885756.9 First in ClinVar: Feb 18, 2019 Last updated: Feb 20, 2024
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000303200.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Oct 09, 2014)	criteria provided, single submitter (ACGS Guidelines, 2013) Method: clinical testing	Hypertrophic cardiomyopathy 4 Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Study: VKGL Data-share Consensus Accession: SCV000743573.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Benign (Jan 18, 2008)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000059313.5 First in ClinVar: May 03, 2013 Last updated: Oct 02, 2016	Publications: PubMed (4) PubMed: 12110947‚ 12818575‚ 14563344‚ 15519027 Number of individuals with the variant: 1114
Benign (Sep 05, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Left ventricular noncompaction 10 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002014346.1 First in ClinVar: Nov 13, 2021 Last updated: Nov 13, 2021
Benign (Sep 05, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hypertrophic cardiomyopathy 4 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002014347.1 First in ClinVar: Nov 13, 2021 Last updated: Nov 13, 2021
Benign (Feb 05, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hypertrophic cardiomyopathy (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	All of Us Research Program, National Institutes of Health Accession: SCV004834732.1 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)	Number of individuals with the variant: 21730
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005224335.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (-)	no assertion criteria provided Method: clinical testing	Hypertrophic cardiomyopathy 4 Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV000733063.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001920515.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Benign (Oct 03, 2017)	no assertion criteria provided Method: provider interpretation	not provided Affected status: unknown Allele origin: germline	Stanford Center for Inherited Cardiovascular Disease, Stanford University Accession: SCV000924847.1 First in ClinVar: Jul 01, 2019 Last updated: Jul 01, 2019
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001952814.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Benign (Oct 10, 2022)	no assertion criteria provided (ACMG Guidelines, 2015) Method: clinical testing	Hypertrophic cardiomyopathy Affected status: yes Allele origin: germline	Cohesion Phenomics Accession: SCV003800609.2 First in ClinVar: Feb 13, 2023 Last updated: Apr 15, 2023
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Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Comment:

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
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
Identification of the genotypes causing hypertrophic cardiomyopathy in northern Sweden.	Mörner S	Journal of molecular and cellular cardiology	2003	PMID: 12818575
Mutations in the cardiac myosin-binding protein C gene are the predominant cause of familial hypertrophic cardiomyopathy in eastern Finland.	Jääskeläinen P	Journal of molecular medicine (Berlin, Germany)	2002	PMID: 12110947
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MYBPC3	-	-	-	-

Text-mined citations for rs3729989 ...

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 Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_000256.3(MYBPC3):c.706A>G (p.Ser236Gly)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs3729989 ...