NM_000257.4(MYH7):c.2770G>A (p.Glu924Lys) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 18, 2021
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:: RCV000252292.4

Allele description [Variation Report for NM_000257.4(MYH7):c.2770G>A (p.Glu924Lys)]

NM_000257.4(MYH7):c.2770G>A (p.Glu924Lys)

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.2770G>A (p.Glu924Lys)

Other names:

p.E924K:GAG>AAG

HGVS:

NC_000014.9:g.23424059C>T
NG_007884.1:g.16603G>A
NM_000257.4:c.2770G>AMANE SELECT
NP_000248.2:p.Glu924Lys
LRG_384t1:c.2770G>A
LRG_384:g.16603G>A
NC_000014.8:g.23893268C>T
NM_000257.2:c.2770G>A
NM_000257.3:c.2770G>A
P12883:p.Glu924Lys
c.2770G>A

Protein change:

E924K; GLU924LYS

Links:

UniProtKB: P12883#VAR_004594; OMIM: 160760.0006; dbSNP: rs121913628

NCBI 1000 Genomes Browser:

rs121913628

Molecular consequence:

NM_000257.4:c.2770G>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
SCV000319014	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Oct 18, 2021)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 10024460, 1430197, 16630449, 18403758, 18409188, 22429680, 24510615, 25351510, 27532257 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000319014

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Oct 18, 2021)

germline

clinical testing

PubMed (9)
[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

Mutations in beta-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin-binding protein-C.

Gruen M, Gautel M.

J Mol Biol. 1999 Feb 26;286(3):933-49.

PubMed [citation]

PMID:: 10024460

Sporadic hypertrophic cardiomyopathy due to de novo myosin mutations.

Watkins H, Thierfelder L, Hwang DS, McKenna W, Seidman JG, Seidman CE.

J Clin Invest. 1992 Nov;90(5):1666-71.

PubMed [citation]

PMID:: 1430197
PMCID:: PMC443222

See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV000319014.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

The p.E924K pathogenic mutation (also known as c.2770G>A), located in coding exon 21 of the MYH7 gene, results from a G to A substitution at nucleotide position 2770. The glutamic acid at codon 924 is replaced by lysine, an amino acid with similar properties. This alteration has been reported across ethnicities in individuals with hypertrophic cardiomyopathy (HCM), including at least two de novo cases (Watkins H et al. J. Clin. Invest., 1992 Nov;90:1666-71; Morita H et al. N. Engl. J. Med., 2008 May;358:1899-908; Fokstuen S et al. Hum. Mutat., 2008 Jun;29:879-85; Santos S et al. BMC Med. Genet., 2012 Mar;13:17). Segregation with disease in affected family members has also been described (Watkins H et al. J. Clin. Invest., 1992 Nov;90:1666-71; Liu WL et al. Zhonghua Xin Xue Guan Bing Za Zhi, 2006 Mar;34:202-7). Additionally, this alteration has been reported in HCM cohorts, although clinical details were limited (Kapplinger JD et al. J Cardiovasc Transl Res. 2014;7(3):347-61; Lopes LR et al. Heart, 2015 Feb;101:294-301; Walsh R et al. Genet. Med., 2017 Feb;19:192-203). Functional studies in rat cardiomyocytes have shown no apparent structural changes, but total loss of MyBP-C binding was observed (Gruen M. J. Mol. Biol. 1999 Feb;286:933-949). 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: Oct 13, 2024

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