NM_000257.4(MYH7):c.3158G>A (p.Arg1053Gln) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 27, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000621026.3

Allele description [Variation Report for NM_000257.4(MYH7):c.3158G>A (p.Arg1053Gln)]

NM_000257.4(MYH7):c.3158G>A (p.Arg1053Gln)

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.3158G>A (p.Arg1053Gln)

Other names:

p.R1053Q:CGG>CAG; NM_000257.3(MYH7):c.3158G>A; NM_000257.4(MYH7):c.3158G>A

HGVS:

NC_000014.9:g.23422267C>T
NG_007884.1:g.18395G>A
NM_000257.4:c.3158G>AMANE SELECT
NP_000248.2:p.Arg1053Gln
LRG_384t1:c.3158G>A
LRG_384:g.18395G>A
NC_000014.8:g.23891476C>T
NM_000257.2:c.3158G>A
NM_000257.3:c.3158G>A

Protein change:

R1053Q

Links:

dbSNP: rs587782962

NCBI 1000 Genomes Browser:

rs587782962

Molecular consequence:

NM_000257.4:c.3158G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000739917	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (May 27, 2022)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 15556047, 20624503, 20800588, 24888384, 27532257, 29300372, 30775854, 31737537, 32960281, 33673806, 34615813 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000739917

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(May 27, 2022)

germline

clinical testing

PubMed (11)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Two novel mutations in the beta-myosin heavy chain gene associated with dilated cardiomyopathy.

Kärkkäinen S, Heliö T, Jääskeläinen P, Miettinen R, Tuomainen P, Ylitalo K, Kaartinen M, Reissell E, Toivonen L, Nieminen MS, Kuusisto J, Laakso M, Peuhkurinen K.

Eur J Heart Fail. 2004 Dec;6(7):861-8.

PubMed [citation]

PMID:: 15556047

Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy.

Millat G, Bouvagnet P, Chevalier P, Dauphin C, Jouk PS, Da Costa A, Prieur F, Bresson JL, Faivre L, Eicher JC, Chassaing N, Crehalet H, Porcher R, Rodriguez-Lafrasse C, Rousson R.

Eur J Med Genet. 2010 Sep-Oct;53(5):261-7. doi: 10.1016/j.ejmg.2010.07.007. Epub 2010 Jul 30.

PubMed [citation]

PMID:: 20624503

See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV000739917.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

The p.R1053Q pathogenic mutation (also known as c.3158G>A), located in coding exon 23 of the MYH7 gene, results from a G to A substitution at nucleotide position 3158. The arginine at codon 1053 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in numerous individuals with hypertrophic cardiomyopathy (HCM), including segregating with disease in one family (Kärkkäinen S, Eur. J. Heart Fail. 2004 Dec; 6(7):861-8; Millat G et al. Eur J Med Genet Jul;53:261-7; Walsh R et al. Genet Med, 2017 02;19:192-203; Kelly MA et al. Genet Med, 2018 03;20:351-359; Jääskeläinen P et al. ESC Heart Fail, 2019 Apr;6:436-445; Marschall C et al. Cardiovasc Diagn Ther, 2019 Oct;9:S292-S298; Costain G et al. JAMA Netw Open, 2020 09;3:e2018109; Yoshinaga M et al. Circ J, 2021 12;86:118-127; Hathaway J et al. BMC Cardiovasc Disord, 2021 03;21:126). This alteration has also been described as a founder mutation in a Finnish HCM cohort, accounting for approximately 5-8% of MYH7 variants detected (Jääskeläinen P et al. Ann. Med., 2014 Sep;46:424-9; Jääskeläinen P et al. ESC Heart Fail, 2019 Apr;6:436-445). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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