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NM_000257.4(MYH7):c.767G>A (p.Gly256Glu) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 5, 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:
RCV002399324.2

Allele description [Variation Report for NM_000257.4(MYH7):c.767G>A (p.Gly256Glu)]

NM_000257.4(MYH7):c.767G>A (p.Gly256Glu)

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.767G>A (p.Gly256Glu)
Other names:
p.G256E:GGA>GAA
HGVS:
  • NC_000014.9:g.23431447C>T
  • NG_007884.1:g.9215G>A
  • NM_000257.4:c.767G>AMANE SELECT
  • NP_000248.2:p.Gly256Glu
  • LRG_384t1:c.767G>A
  • LRG_384:g.9215G>A
  • NC_000014.8:g.23900656C>T
  • NM_000257.2:c.767G>A
  • NM_000257.3:c.767G>A
  • P12883:p.Gly256Glu
  • c.767G>A
Protein change:
G256E; GLY256GLU
Links:
UniProtKB: P12883#VAR_004570; OMIM: 160760.0012; dbSNP: rs121913633
NCBI 1000 Genomes Browser:
rs121913633
Molecular consequence:
  • NM_000257.4:c.767G>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
SCV002673154Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Oct 5, 2022) 		germlineclinical testing

PubMed (6)
[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

Development and validation of a computational method for assessment of missense variants in hypertrophic cardiomyopathy.

Jordan DM, Kiezun A, Baxter SM, Agarwala V, Green RC, Murray MF, Pugh T, Lebo MS, Rehm HL, Funke BH, Sunyaev SR.

Am J Hum Genet. 2011 Feb 11;88(2):183-92. doi: 10.1016/j.ajhg.2011.01.011.

PubMed [citation]
PMID:
21310275
PMCID:
PMC3035712

Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy.

Lopes LR, Syrris P, Guttmann OP, O'Mahony C, Tang HC, Dalageorgou C, Jenkins S, Hubank M, Monserrat L, McKenna WJ, Plagnol V, Elliott PM.

Heart. 2015 Feb;101(4):294-301. doi: 10.1136/heartjnl-2014-306387. Epub 2014 Oct 28.

PubMed [citation]
PMID:
25351510
PMCID:
PMC4345808
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002673154.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

The p.G256E pathogenic mutation (also known as c.767G>A), located in coding exon 7 of the MYH7 gene, results from a G to A substitution at nucleotide position 767. The glycine at codon 256 is replaced by glutamic acid, an amino acid with similar properties. This alteration is located in the myosin head domain, which contains a statistically significant clustering of pathogenic missense variants (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 detected in a large family with hypertrophic cardiomyopathy (HCM) and segregation with disease in numerous family members (Fananapazir L et al. Proc. Natl. Acad. Sci. U.S.A., 1993 May;90:3993-7; Fananapazir L et al. Circulation, 1994 Jan;89:22-32). This alteration has also been reported in HCM cohorts; however, clinical details were limited (Lopes LR et al. Heart, 2015 Feb;101:294-301; Walsh R et al. Genet. Med., 2017 02;19:192-203). Functional studies in soleus muscle cells with this alteration demonstrated slower movement of actin filaments compared to wild-type controls (Cuda G et al. J. Muscle Res. Cell. Motil., 1997 Jun;18:275-83). 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 BayesDel in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024