NM_000257.4(MYH7):c.2287G>A (p.Val763Met) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 28, 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:: RCV002444635.2

Allele description [Variation Report for NM_000257.4(MYH7):c.2287G>A (p.Val763Met)]

NM_000257.4(MYH7):c.2287G>A (p.Val763Met)

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.2287G>A (p.Val763Met)

HGVS:

NC_000014.9:g.23425418C>T
NG_007884.1:g.15244G>A
NM_000257.4:c.2287G>AMANE SELECT
NP_000248.2:p.Val763Met
LRG_384t1:c.2287G>A
LRG_384:g.15244G>A
NC_000014.8:g.23894627C>T
NM_000257.2:c.2287G>A
NM_000257.3:c.2287G>A
P12883:p.Val763Met

Protein change:

V763M

Links:

UniProtKB: P12883#VAR_045926; dbSNP: rs727504253

NCBI 1000 Genomes Browser:

rs727504253

Molecular consequence:

NM_000257.4:c.2287G>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
SCV002735530	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 28, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18403758, 26743238, 27532257, 28606303, 31582565 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002735530

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 28, 2021)

germline

clinical testing

PubMed (5)
[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

Shared genetic causes of cardiac hypertrophy in children and adults.

Morita H, Rehm HL, Menesses A, McDonough B, Roberts AE, Kucherlapati R, Towbin JA, Seidman JG, Seidman CE.

N Engl J Med. 2008 May 1;358(18):1899-908. doi: 10.1056/NEJMoa075463. Epub 2008 Apr 9.

PubMed [citation]

PMID:: 18403758
PMCID:: PMC2752150

Patient Outcomes From a Specialized Inherited Arrhythmia Clinic.

Adler A, Sadek MM, Chan AY, Dell E, Rutberg J, Davis D, Green MS, Spears DA, Gollob MH.

Circ Arrhythm Electrophysiol. 2016 Jan;9(1):e003440. doi: 10.1161/CIRCEP.115.003440.

PubMed [citation]

PMID:: 26743238

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV002735530.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The p.V763M variant (also known as c.2287G>A) is located in coding exon 19 of the MYH7 gene. The valine at codon 763 is replaced by methionine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 19. 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 has been detected in a pediatric hypertrophic cardiomyopathy patient who also carried a pathogenic mutation in MYH7 (Morita H et al. N. Engl. J. Med. 2008;358:1899-908). This variant has also been reported in an HCM cohort and in an arrhythmia cohort; however, clinical details were limited (Adler A et al. Circ Arrhythm Electrophysiol. 2016;9:e003440; Walsh R et al. Genet. Med. 2017;19:192-203). 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.

#	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: May 1, 2024

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