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NM_000257.4(MYH7):c.5329G>A (p.Ala1777Thr) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 6, 2024
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:
RCV000620826.5

Allele description [Variation Report for NM_000257.4(MYH7):c.5329G>A (p.Ala1777Thr)]

NM_000257.4(MYH7):c.5329G>A (p.Ala1777Thr)

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.5329G>A (p.Ala1777Thr)
Other names:
NM_000257.3(MYH7):c.5329G>A
HGVS:
  • NC_000014.9:g.23415225C>T
  • NG_007884.1:g.25437G>A
  • NM_000257.4:c.5329G>AMANE SELECT
  • NP_000248.2:p.Ala1777Thr
  • LRG_384t1:c.5329G>A
  • LRG_384:g.25437G>A
  • NC_000014.8:g.23884434C>T
  • NM_000257.2:c.5329G>A
  • NM_000257.3:c.5329G>A
  • P12883:p.Ala1777Thr
Protein change:
A1777T
Links:
UniProtKB: P12883#VAR_019871; dbSNP: rs200939753
NCBI 1000 Genomes Browser:
rs200939753
Molecular consequence:
  • NM_000257.4:c.5329G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000739971Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Nov 6, 2024) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy.

Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M; EUROGENE Heart Failure Project.

Circulation. 2003 May 6;107(17):2227-32. Epub 2003 Apr 21. Erratum in: Circulation. 2004 Jun 29;109(25):3258.

PubMed [citation]
PMID:
12707239

Interpreting secondary cardiac disease variants in an exome cohort.

Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program.

Circ Cardiovasc Genet. 2013 Aug;6(4):337-46. doi: 10.1161/CIRCGENETICS.113.000039. Epub 2013 Jul 16.

PubMed [citation]
PMID:
23861362
PMCID:
PMC3887521
See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV000739971.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

The p.A1777T variant (also known as c.5329G>A), located in coding exon 35 of the MYH7 gene, results from a G to A substitution at nucleotide position 5329. The alanine at codon 1777 is replaced by threonine, an amino acid with similar properties. This variant has been reported in individuals with hypertrophic cardiomyopathy (HCM) (Richard P et al. Circulation. 2003;107(17):2227-32); Bos JM et al. Mayo Clin. Proc., 2014 Jun;89:727-37; Homburger JR et al. Proc. Natl. Acad. Sci. U.S.A., 2016 06;113:6701-6; Walsh R et al. Genet. Med., 2017 02;19:192-203; Ambry internal data). This alteration was also identified in a patient reported to have distal and axial myopathy, and a patient reported to have myofibrillar myopathy (Evilä A et al. Neuromuscul Disord. 2016;26(1):7-15; Chanson JB et al. Eur J Neurol. 2016; 23(6):1086-92). This variant has been detected in a case with Brugada syndrome and co-occurred with MYBPC3 variants in an individual with noncompaction cardiomyopathy (Hertz CL et al. Int. J. Legal Med., 2015 Jul;129:793-800; Liu S et al. Int J Cardiol. 2020 03;302:117-123). This variant has also been detected in individuals from a cohort not indicated as having cardiomyopathy or skeletal myopathy; however, details were limited (Park J et al. Hum Mol Genet. 2022 03;31(5):827-837). This alteration has been reported as a secondary cardiac variant in an exome cohort (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: May 16, 2025