U.S. flag

An official website of the United States government

NM_000257.4(MYH7):c.3475G>A (p.Val1159Met) AND Cardiomyopathy

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Dec 1, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003531997.3

Allele description [Variation Report for NM_000257.4(MYH7):c.3475G>A (p.Val1159Met)]

NM_000257.4(MYH7):c.3475G>A (p.Val1159Met)

Gene:
MYH7:myosin heavy chain 7 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q11.2
Genomic location:
Preferred name:
NM_000257.4(MYH7):c.3475G>A (p.Val1159Met)
Other names:
p.V1159M:GTG>ATG
HGVS:
  • NC_000014.9:g.23420096C>T
  • NG_007884.1:g.20566G>A
  • NM_000257.4:c.3475G>AMANE SELECT
  • NP_000248.2:p.Val1159Met
  • LRG_384t1:c.3475G>A
  • LRG_384:g.20566G>A
  • NC_000014.8:g.23889305C>T
  • NM_000257.2:c.3475G>A
  • NM_000257.3:c.3475G>A
Protein change:
V1159M
Links:
dbSNP: rs730880776
NCBI 1000 Genomes Browser:
rs730880776
Molecular consequence:
  • NM_000257.4:c.3475G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
14

Condition(s)

Name:
Cardiomyopathy (CMYO)
Synonyms:
Cardiomyopathies
Identifiers:
MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004356867Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Sep 26, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004814580All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Dec 1, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown14not providednot provided108544not providedclinical testing

Citations

PubMed

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]
PMID:
27532257
PMCID:
PMC5116235

Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity.

Harper AR, Goel A, Grace C, Thomson KL, Petersen SE, Xu X, Waring A, Ormondroyd E, Kramer CM, Ho CY, Neubauer S; HCMR Investigators., Tadros R, Ware JS, Bezzina CR, Farrall M, Watkins H.

Nat Genet. 2021 Feb;53(2):135-142. doi: 10.1038/s41588-020-00764-0. Epub 2021 Jan 25.

PubMed [citation]
PMID:
33495597
PMCID:
PMC8240954
See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV004356867.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This missense variant replaces valine with methionine at codon 1159 of the MYH7 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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: 27532257, 33495597). This variant has not been identified 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004814580.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided14not providednot providedclinical testing PubMed (3)

Description

This missense variant replaces valine with methionine at codon 1159 of the MYH7 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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: 27532257, 33495597). This variant has not been identified 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided14not providednot providednot provided

Last Updated: Sep 29, 2024