VCV000181297.36 - ClinVar

NM_000257.4(MYH7):c.211G>A (p.Val71Met)

Germline

Classification

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

Uncertain significance

10 out of 10 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_000257.4(MYH7):c.211G>A (p.Val71Met)

Variation ID: 181297 Accession: VCV000181297.36

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 14q11.2 14: 23433218 (GRCh38) [ NCBI UCSC ] 14: 23902427 (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	Jan 11, 2026	Dec 20, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000257.4:c.211G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000248.2:p.Val71Met	missense
NC_000014.9:g.23433218C>T
NC_000014.8:g.23902427C>T
NG_007884.1:g.7444G>A
LRG_384:g.7444G>A
LRG_384t1:c.211G>A

... more HGVS ... less HGVS

Protein change

V71M

Other names

p.V71M:GTG>ATG

Canonical SPDI

NC_000014.9:23433217:C: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.

The Genome Aggregation Database (gnomAD) 0.00004

The Genome Aggregation Database (gnomAD), exomes 0.00005

Trans-Omics for Precision Medicine (TOPMed) 0.00007

Exome Aggregation Consortium (ExAC) 0.00004

Links

ClinGen: CA011723 dbSNP: rs730880830 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.
MYH7		No evidence available	No evidence available	GRCh38 GRCh37	4298	5794

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	Dec 20, 2025	RCV000168833.24
Hypertrophic cardiomyopathy	Uncertain significance (1)	criteria provided, single submitter	Jan 2, 2024	RCV000537548.8
not specified	Uncertain significance (1)	criteria provided, single submitter	Jan 6, 2020	RCV001174729.1
Cardiomyopathy	Uncertain significance (3)	criteria provided, multiple submitters, no conflicts	Jul 20, 2024	RCV001180300.10
Congenital myopathy with fiber type disproportion Dilated cardiomyopathy 1S Hypertrophic cardiomyopathy 1 MYH7-related skeletal myopathy Myopathy, myosin storage, autosomal recessive Myosin storage myopathy	Uncertain significance (1)	criteria provided, single submitter	Sep 8, 2021	RCV002484983.1
Cardiovascular phenotype	Uncertain significance (1)	criteria provided, single submitter	May 19, 2025	RCV003298186.3

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 (Jan 06, 2020) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	not specified	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV001338008.1 First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020	Comment: show Variant summary: MYH7 c.211G>A (p.Val71Met) results in a conservative amino acid change located in the Myosin, N-terminal, SH3-like domain (IPR004009) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-05 in 251330 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in MYH7 causing Cardiomyopathy (5.2e-05 vs 0.0013), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.211G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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 (Sep 10, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cardiomyopathy	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Accession: SCV003838775.1 First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023	Publications: PubMed (1) PubMed: 25741868 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 (Jul 20, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cardiomyopathy (Autosomal dominant inheritance)	All of Us Research Program, National Institutes of Health Accession: SCV004822768.2 First in ClinVar: Apr 20, 2024 Last updated: Dec 14, 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)	Comment: show This missense variant replaces valine with methionine at codon 71 of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 14/282710 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 Number of individuals with the variant: 27 Zygosity: Single Heterozygote

Uncertain significance (Jan 30, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cardiomyopathy	Color Diagnostics, LLC DBA Color Health Accession: SCV001345195.4 First in ClinVar: Jun 22, 2020 Last updated: May 03, 2025	Publications: PubMed (1) PubMed: 34490048 Comment: show This missense variant replaces valine with methionine at codon 71 of the MYH7 protein. Computational prediction tools indicate that this variant's impact on protein structure and function is inconclusive. To our knowledge, functional studies have not been reported for this variant. This variant has been reported one infant affected with enlarged left ventricle and reduced systolic and diastolic function (PMID: 34490048). This variant has been identified in 14/282710 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 (May 19, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cardiovascular phenotype	Ambry Genetics Accession: SCV003993400.3 First in ClinVar: Jul 08, 2023 Last updated: Jul 13, 2025	Publications: PubMed (3) PubMed: 33954932‚ 34490048‚ 37652022 Comment: show The p.V71M variant (also known as c.211G>A), located in coding exon 2 of the MYH7 gene, results from a G to A substitution at nucleotide position 211. The valine at codon 71 is replaced by methionine, an amino acid with highly similar properties. This variant was reported in individual(s) with features consistent with MYH7-related cardiomyopathy (Ouyang X et al. Front Genet, 2021 Aug;12:725259; McGurk KA et al. Am J Hum Genet. 2023 Sep;110(9):1482-1495). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. (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 (Sep 24, 2020) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided	Revvity Omics, Revvity Accession: SCV003817770.3 First in ClinVar: Mar 04, 2023 Last updated: Sep 06, 2025	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 (Dec 20, 2025) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Not Provided	GeneDx Accession: SCV000208660.12 First in ClinVar: Feb 24, 2015 Last updated: Dec 27, 2025	Comment: show In silico analysis suggests that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34542152, 37652022, 34490048) (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 (Sep 08, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	MYH7-related skeletal myopathy Myosin storage myopathy Hypertrophic cardiomyopathy 1 Myopathy, myosin storage, autosomal recessive Congenital myopathy 4A, autosomal dominant Myosin storage myopathy Dilated cardiomyopathy 1S	Fulgent Genetics, Fulgent Genetics Accession: SCV002794459.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Uncertain significance (Jan 02, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Hypertrophic cardiomyopathy	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000623659.7 First in ClinVar: Dec 26, 2017 Last updated: Feb 14, 2024	Publications: PubMed (2) PubMed: 28492532‚ 34490048 Comment: show This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 71 of the MYH7 protein (p.Val71Met). This variant is present in population databases (rs730880830, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of dilated cardiomyopathy (PMID: 34490048; Invitae). ClinVar contains an entry for this variant (Variation ID: 181297). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function with a positive predictive value of 95%. 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 (Jun 01, 2024) 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: SCV005075744.14 First in ClinVar: Jul 15, 2024 Last updated: Jan 11, 2026	Comment: show MYH7: PM2 (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:

Variant summary: MYH7 c.211G>A (p.Val71Met) results in a conservative amino acid change located in the Myosin, N-terminal, SH3-like domain (IPR004009) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-05 in 251330 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in MYH7 causing Cardiomyopathy (5.2e-05 vs 0.0013), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.211G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

Comment:

This missense variant replaces valine with methionine at codon 71 of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 14/282710 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 missense variant replaces valine with methionine at codon 71 of the MYH7 protein. Computational prediction tools indicate that this variant's impact on protein structure and function is inconclusive. To our knowledge, functional studies have not been reported for this variant. This variant has been reported one infant affected with enlarged left ventricle and reduced systolic and diastolic function (PMID: 34490048). This variant has been identified in 14/282710 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:

The p.V71M variant (also known as c.211G>A), located in coding exon 2 of the MYH7 gene, results from a G to A substitution at nucleotide position 211. The valine at codon 71 is replaced by methionine, an amino acid with highly similar properties. This variant was reported in individual(s) with features consistent with MYH7-related cardiomyopathy (Ouyang X et al. Front Genet, 2021 Aug;12:725259; McGurk KA et al. Am J Hum Genet. 2023 Sep;110(9):1482-1495). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

Comment:

This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 71 of the MYH7 protein (p.Val71Met). This variant is present in population databases (rs730880830, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of dilated cardiomyopathy (PMID: 34490048; Invitae). ClinVar contains an entry for this variant (Variation ID: 181297). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function with a positive predictive value of 95%. 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
Clinical Utility of Rapid Exome Sequencing Combined With Mitochondrial DNA Sequencing in Critically Ill Pediatric Patients With Suspected Genetic Disorders.	Ouyang X	Frontiers in genetics	2021	PMID: 34490048
Molecular Diagnosis of Inherited Cardiac Diseases in the Era of Next-Generation Sequencing: A Single Center's Experience Over 5 Years.	Janin A	Molecular diagnosis & therapy	2021	PMID: 33954932
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.	Richards S	Genetics in medicine : official journal of the American College of Medical Genetics	2015	PMID: 25741868

Text-mined citations for rs730880830 ...

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 Jan 11, 2026