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NM_000257.4(MYH7):c.4985G>A (p.Arg1662His) AND Cardiomyopathy

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
Aug 8, 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:
RCV001184540.8

Allele description [Variation Report for NM_000257.4(MYH7):c.4985G>A (p.Arg1662His)]

NM_000257.4(MYH7):c.4985G>A (p.Arg1662His)

Genes:
LOC126861897:BRD4-independent group 4 enhancer GRCh37_chr14:23884455-23885654 [Gene]
MYH7:myosin heavy chain 7 [Gene - OMIM - HGNC]
MHRT:myosin heavy chain associated RNA transcript [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q11.2
Genomic location:
Preferred name:
NM_000257.4(MYH7):c.4985G>A (p.Arg1662His)
Other names:
p.R1662H:CGT>CAT
HGVS:
  • NC_000014.9:g.23415801C>T
  • NG_007884.1:g.24861G>A
  • NM_000257.4:c.4985G>AMANE SELECT
  • NP_000248.2:p.Arg1662His
  • LRG_384t1:c.4985G>A
  • LRG_384:g.24861G>A
  • NC_000014.8:g.23885010C>T
  • NM_000257.2:c.4985G>A
  • NM_000257.3:c.4985G>A
  • NR_126491.1:n.233C>T
  • c.4985G>A
Protein change:
R1662H
Links:
dbSNP: rs370328209
NCBI 1000 Genomes Browser:
rs370328209
Molecular consequence:
  • NM_000257.4:c.4985G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_126491.1:n.233C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
2

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001350548Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Feb 23, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV002042688CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(May 4, 2020) 		germlineclinical testing

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

SCV004814363All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Aug 8, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown2not providednot provided108544not providedclinical testing

Citations

PubMed

Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure.

Waldmüller S, Erdmann J, Binner P, Gelbrich G, Pankuweit S, Geier C, Timmermann B, Haremza J, Perrot A, Scheer S, Wachter R, Schulze-Waltrup N, Dermintzoglou A, Schönberger J, Zeh W, Jurmann B, Brodherr T, Börgel J, Farr M, Milting H, Blankenfeldt W, Reinhardt R, et al.

Eur J Heart Fail. 2011 Nov;13(11):1185-92. doi: 10.1093/eurjhf/hfr074. Epub 2011 Jul 12.

PubMed [citation]
PMID:
21750094

Early results of sarcomeric gene screening from the Egyptian National BA-HCM Program.

Kassem HSh, Azer RS, Saber-Ayad M, Moharem-Elgamal S, Magdy G, Elguindy A, Cecchi F, Olivotto I, Yacoub MH.

J Cardiovasc Transl Res. 2013 Feb;6(1):65-80. doi: 10.1007/s12265-012-9425-0. Epub 2012 Dec 12. Erratum in: J Cardiovasc Transl Res. 2013 Aug;6(4):663. Ayad, Maha S [corrected to Saber-Ayad, Maha].

PubMed [citation]
PMID:
23233322
PMCID:
PMC3546296
See all PubMed Citations (7)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001350548.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This missense variant replaces arginine with histidine at codon 1662 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 been reported in four individuals affected with hypertrophic cardiomyopathy (PMID: 23233322, 27532257, 31638223, 34137518, 33495597). However, one of these individuals also harbored a splice site variant in the MYBPC3 gene that was associated with disease in the family (PMID: 23233322), and another individual is a carrier of a pathogenic co-variant MYH7 c.2081G>A (p.Arg694His) (ClinVar Variation ID: 264068). This variant has also been reported in one individual affected with dilated cardiomyopathy (PMID: 21750094). This variant has been identified in 16/282816 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.

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

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV002042688.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004814363.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (7)

Description

This missense variant replaces arginine with histidine at codon 1662 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 been reported in four individuals affected with hypertrophic cardiomyopathy (PMID: 23233322, 27532257, 31638223, 34137518, 33495597). However, one of these individuals also harbored a splice site variant in the MYBPC3 gene that was associated with disease in the family (PMID: 23233322), and another individual is a carrier of a pathogenic co-variant MYH7 c.2081G>A (p.Arg694His) (ClinVar Variation ID: 264068). This variant has also been reported in one individual affected with dilated cardiomyopathy (PMID: 21750094). This variant has been identified in 16/282816 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided2not providednot providednot provided

Last Updated: Sep 29, 2024