NM_000257.4(MYH7):c.2302G>A (p.Gly768Arg) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 4, 2017
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:: RCV000151276.7

Allele description [Variation Report for NM_000257.4(MYH7):c.2302G>A (p.Gly768Arg)]

NM_000257.4(MYH7):c.2302G>A (p.Gly768Arg)

Genes:

LOC126861898:BRD4-independent group 4 enhancer GRCh37_chr14:23893609-23894808 [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.2302G>A (p.Gly768Arg)

Other names:

p.G768R:GGG>AGG

HGVS:

NC_000014.9:g.23425403C>T
NG_007884.1:g.15259G>A
NM_000257.4:c.2302G>AMANE SELECT
NP_000248.2:p.Gly768Arg
LRG_384t1:c.2302G>A
LRG_384:g.15259G>A
NC_000014.8:g.23894612C>T
NM_000257.2:c.2302G>A
NM_000257.3:c.2302G>A
P12883:p.Gly768Arg

Protein change:

G768R

Links:

UniProtKB: P12883#VAR_019859; dbSNP: rs727503260

NCBI 1000 Genomes Browser:

rs727503260

Molecular consequence:

NM_000257.4:c.2302G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Restrictive cardiomyopathy
Identifiers:: MONDO: MONDO:0005201; MeSH: D002313; MedGen: C0007196; Human Phenotype Ontology: HP:0001723

Name:: Hypertrophic cardiomyopathy
Synonyms:: HYPERTROPHIC MYOCARDIOPATHY
Identifiers:: MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000199202	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Sep 4, 2017)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 12707239, 20394946, 18076673, 22260945, 17125710, 23690394, 25524337, 20800588, 23549607, 25935763, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000199202

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Sep 4, 2017)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	16	7	not provided	not provided	not provided	clinical 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

A fetus with hypertrophic cardiomyopathy, restrictive, and single-ventricle physiology, and a beta-myosin heavy chain mutation.

Hinton RB, Michelfelder EC, Marino BS, Bove KE, Ware SM.

J Pediatr. 2010 Jul;157(1):164-6. doi: 10.1016/j.jpeds.2010.02.044. Epub 2010 Apr 14.

PubMed [citation]

PMID:: 20394946
PMCID:: PMC2886151

See all PubMed Citations (11)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000199202.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	16	not provided	not provided	clinical testing	PubMed (11)

Description

The p.Gly768Arg variant in MYH7 has been reported in 13 individuals with HCM, HC M with RCM, HCM with LVNC, or RCM, and segregated with disease in 5 affected rel atives from 3 families (Richard 2003, Laredo 2006, Ware 2008, Hinton 2010, Ho 20 13, Walsh 2014, Coppini 2014, Garcia-Giustiniani 2015, LMM data). It has not bee n identified in large population studies. Glycine (Gly) at position 768 is highl y conserved in mammals and across evolutionarily distant species and the change to arginine (Arg) was predicted to be pathogenic using a computational tool clin ically validated by our laboratory. This tool's pathogenic prediction is estimat ed to be correct 94% of the time (Jordan 2011). In summary, this variant meets c riteria to be classified as pathogenic for cardiomyopathy in an autosomal domina nt manner based upon prevalence in affected probands, segregation with disease, predicted functional impact, and extremely low frequency in the general populati on.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		16	not provided	7	not provided

Last Updated: Oct 20, 2024

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