NM_000257.4(MYH7):c.1208G>T (p.Arg403Leu) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 23, 2020
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:: RCV002345243.2

Allele description [Variation Report for NM_000257.4(MYH7):c.1208G>T (p.Arg403Leu)]

NM_000257.4(MYH7):c.1208G>T (p.Arg403Leu)

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.1208G>T (p.Arg403Leu)

Other names:

p.R403L:CGG>CTG

HGVS:

NC_000014.9:g.23429278C>A
NG_007884.1:g.11384G>T
NM_000257.4:c.1208G>TMANE SELECT
NP_000248.2:p.Arg403Leu
LRG_384t1:c.1208G>T
LRG_384:g.11384G>T
LRG_384p1:p.Arg403Leu
NC_000014.8:g.23898487C>A
NM_000257.2:c.1208G>T
P12883:p.Arg403Leu

Protein change:

R403L; ARG403LEU

Links:

UniProtKB: P12883#VAR_004573; OMIM: 160760.0014; dbSNP: rs121913624

NCBI 1000 Genomes Browser:

rs121913624

Molecular consequence:

NM_000257.4:c.1208G>T - 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
SCV002648499	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jul 23, 2020)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 15386449, 22429680, 27532257, 31006259, 31722741, 7848420, 8254035 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002648499

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jul 23, 2020)

germline

clinical testing

PubMed (7)
[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

Prenatal molecular diagnosis in hypertrophic cardiomyopathy: report of the first case.

Charron P, Héron D, Gargiulo M, Feingold J, Oury JF, Richard P, Komajda M.

Prenat Diagn. 2004 Sep;24(9):701-3.

PubMed [citation]

PMID:: 15386449

High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort.

Santos S, Marques V, Pires M, Silveira L, Oliveira H, Lança V, Brito D, Madeira H, Esteves JF, Freitas A, Carreira IM, Gaspar IM, Monteiro C, Fernandes AR.

BMC Med Genet. 2012 Mar 19;13:17. doi: 10.1186/1471-2350-13-17.

PubMed [citation]

PMID:: 22429680
PMCID:: PMC3359199

See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV002648499.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The p.R403L pathogenic mutation (also known as c.1208G>T), located in coding exon 11 of the MYH7 gene, results from a G to T substitution at nucleotide position 1208. The arginine at codon 403 is replaced by leucine, an amino acid with dissimilar properties, and is located in the head domain. This variant has been reported in several unrelated individuals with hypertrophic cardiomyopathy (HCM), and has been reported to segregate with disease in families (Dausse E et al. J. Clin. Invest., 1993 Dec;92:2807-13; al-Mahdawi S et al. Br Heart J, 1994 Aug;72:105-11; Santos S et al. BMC Med. Genet. 2012 Mar;13:17; Walsh R et al. Genet. Med., 2017 02;19:192-203; Cui H et al. Orphanet J Rare Dis. 2019 11;14(1):252; Norrish G et al. Circulation, 2019 07;140:184-192). In addition, other pathogenic variants affecting this codon (p.R403Q, c.1208G>A and p.R403W, c.1207C>T) have also been reported in association with HCM (Dausse E et al. J. Clin. Invest., 1993 Dec;92:2807-13; Van Driest SL et al. J. Am. Coll. Cardiol., 2004 Aug;44:602-10). 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: May 1, 2024

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