U.S. flag

An official website of the United States government

NM_000257.4(MYH7):c.1700G>A (p.Arg567His) AND Primary dilated cardiomyopathy

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Sep 27, 2021
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV000035741.8

Allele description [Variation Report for NM_000257.4(MYH7):c.1700G>A (p.Arg567His)]

NM_000257.4(MYH7):c.1700G>A (p.Arg567His)

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.1700G>A (p.Arg567His)
Other names:
NM_000257.4(MYH7):c.1700G>A
HGVS:
  • NC_000014.9:g.23427773C>T
  • NG_007884.1:g.12889G>A
  • NM_000257.4:c.1700G>AMANE SELECT
  • NP_000248.2:p.Arg567His
  • LRG_384t1:c.1700G>A
  • LRG_384:g.12889G>A
  • NC_000014.8:g.23896982C>T
  • NM_000257.2:c.1700G>A
  • NM_000257.3:c.1700G>A
  • c.1700G>A
Protein change:
R567H
Links:
dbSNP: rs377491278
NCBI 1000 Genomes Browser:
rs377491278
Molecular consequence:
  • NM_000257.4:c.1700G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Name:
Primary dilated cardiomyopathy (DCM)
Synonyms:
Dilated Cardiomyopathy
Identifiers:
EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000059392Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)
Likely pathogenic
(Apr 4, 2014)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001976475ClinGen Cardiomyopathy Variant Curation Expert Panel
reviewed by expert panel

(ClinGen CMP ACMG Specifications v1)
Uncertain significance
(Sep 27, 2021)
germlinecuration

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration
not providedgermlinenot provided62not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000059392.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided6not providednot providedclinical testing PubMed (1)

Description

proposed classification - variant undergoing re-assessment, contact laboratory

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided6not provided2not provided

From ClinGen Cardiomyopathy Variant Curation Expert Panel, SCV001976475.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.1700G>A (p.Arg567His) variant in MYH7 has been identified in 3 individuals with DCM, 1 of whom also had an additional variant in another DCM-associated gene (PS4_Supporting; Pugh 2014 PMID:24503780; Walsh 2017 PMID:27532257; GeneDx pers. comm., LMM pers. comm.) and segregated with disease in 3 affected relatives with DCM from 1 family (PP1; LMM pers. comm.). Additionally, this variant has also been reported in an individual with neuropathy and unspecified heart disease who also had an additional variant in a gene that could account for the clinical features observed (Invitae pers. comm.). This variant has been identified in 0.003% (1/30616) of South Asian chromosomes (PM2; http://gnomad.broadinstitute.org, v2.1.1). This variant lies in the head region of the protein (aa 181-937) and while missense variants in this region are statistically more likely to be associated with HCM (Walsh 2017 PMID:27532257), location in this region cannot be used to support pathogenicity for other phenotypes; therefore, PM1 is not applicable. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, due to insufficient evidence, this variant is classified as uncertain significance for dilated cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): PS4_Supporting; PP1; PM2.

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

Last Updated: Jul 15, 2024