NM_000257.4(MYH7):c.5030G>A (p.Arg1677His) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 29, 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:: RCV002336365.2

Allele description [Variation Report for NM_000257.4(MYH7):c.5030G>A (p.Arg1677His)]

NM_000257.4(MYH7):c.5030G>A (p.Arg1677His)

Genes:

LOC126861897:BRD4-independent group 4 enhancer GRCh37_chr14:23884455-23885654 [Gene]
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.5030G>A (p.Arg1677His)

Other names:

p.R1677H:CGC>CAC

HGVS:

NC_000014.9:g.23415756C>T
NG_007884.1:g.24906G>A
NM_000257.4:c.5030G>AMANE SELECT
NP_000248.2:p.Arg1677His
LRG_384t1:c.5030G>A
LRG_384:g.24906G>A
NC_000014.8:g.23884965C>T
NM_000257.2:c.5030G>A
NM_000257.3:c.5030G>A
NR_126491.1:n.188C>T

Protein change:

R1677H

Links:

dbSNP: rs730880914

NCBI 1000 Genomes Browser:

rs730880914

Molecular consequence:

NM_000257.4:c.5030G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_126491.1:n.188C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV002642999	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 29, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 21750094, 24111713, 28807990, 28971120, 30188508 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002642999

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 29, 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

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

Genetics of hypertrophic cardiomyopathy in Norway.

Berge KE, Leren TP.

Clin Genet. 2014 Oct;86(4):355-60. doi: 10.1111/cge.12286. Epub 2013 Oct 23.

PubMed [citation]

PMID:: 24111713

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV002642999.2

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

Description

The p.R1677H variant (also known as c.5030G>A), located in coding exon 33 of the MYH7 gene, results from a G to A substitution at nucleotide position 5030. The arginine at codon 1677 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported in cardiomyopathy cohorts, as well as sudden unexplained death cohorts; however, clinical details were limited (Waldmüller S et al. Eur J Heart Fail, 2011 Nov;13:1185-92; Berge KE et al. Clin Genet, 2014 Oct;86:355-60; Dejgaard LA et al. Data Brief, 2017 Dec;15:30-39; Dewar LJ et al. Circ Cardiovasc Genet, 2017 Aug;10:[ePub ahead of print]; Takasaki A et al. Pediatr Res, 2018 11;84:733-742). 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: Nov 10, 2024

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