NM_000257.4(MYH7):c.4301G>C (p.Arg1434Pro) AND Hypertrophic cardiomyopathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 15, 2019
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:: RCV001036718.8

Allele description [Variation Report for NM_000257.4(MYH7):c.4301G>C (p.Arg1434Pro)]

NM_000257.4(MYH7):c.4301G>C (p.Arg1434Pro)

Genes:

MYH7:myosin heavy chain 7 [Gene - OMIM - HGNC]
MHRT:myosin heavy chain associated RNA transcript [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_000257.4(MYH7):c.4301G>C (p.Arg1434Pro)

HGVS:

NC_000014.9:g.23417555C>G
NG_007884.1:g.23107G>C
NM_000257.4:c.4301G>CMANE SELECT
NP_000248.2:p.Arg1434Pro
LRG_384:g.23107G>C
NC_000014.8:g.23886764C>G
NM_000257.3:c.4301G>C
NR_126491.1:n.836C>G

Protein change:

R1434P

Links:

dbSNP: rs780625785

NCBI 1000 Genomes Browser:

rs780625785

Molecular consequence:

NM_000257.4:c.4301G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_126491.1:n.836C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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
SCV001200095	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 15, 2019)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 21750094, 24119082, 27532257, 21310275, 27519903, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001200095

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 15, 2019)

germline

clinical testing

PubMed (6)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure.

Waldmüller S, Erdmann J, Binner P, Gelbrich G, Pankuweit S, Geier C, Timmermann B, Haremza J, Perrot A, Scheer S, Wachter R, Schulze-Waltrup N, Dermintzoglou A, Schönberger J, Zeh W, Jurmann B, Brodherr T, Börgel J, Farr M, Milting H, Blankenfeldt W, Reinhardt R, et al.

Eur J Heart Fail. 2011 Nov;13(11):1185-92. doi: 10.1093/eurjhf/hfr074. Epub 2011 Jul 12.

PubMed [citation]

PMID:: 21750094

Poor prognosis of rare sarcomeric gene variants in patients with dilated cardiomyopathy.

Merlo M, Sinagra G, Carniel E, Slavov D, Zhu X, Barbati G, Spezzacatene A, Ramani F, Salcedo E, Di Lenarda A, Mestroni L, Taylor MR; Familial Cardiomyopathy Registry..

Clin Transl Sci. 2013 Dec;6(6):424-8. doi: 10.1111/cts.12116. Epub 2013 Oct 3.

PubMed [citation]

PMID:: 24119082
PMCID:: PMC3865161

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001200095.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg1434 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21750094, 24119082, 27532257, 21310275). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has been reported to affect MYH7 protein function (PMID: 27519903). This variant has been observed to segregate with distal myopathy in a family (PMID: 27519903). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 1434 of the MYH7 protein (p.Arg1434Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline.

#	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: Sep 29, 2024

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