NM_000257.4(MYH7):c.5029C>T (p.Arg1677Cys) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 27, 2022
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:: RCV002336359.2

Allele description [Variation Report for NM_000257.4(MYH7):c.5029C>T (p.Arg1677Cys)]

NM_000257.4(MYH7):c.5029C>T (p.Arg1677Cys)

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.5029C>T (p.Arg1677Cys)

Other names:

p.R1677C:CGC>TGC

HGVS:

NC_000014.9:g.23415757G>A
NG_007884.1:g.24905C>T
NM_000257.4:c.5029C>TMANE SELECT
NP_000248.2:p.Arg1677Cys
LRG_384t1:c.5029C>T
LRG_384:g.24905C>T
NC_000014.8:g.23884966G>A
NM_000257.2:c.5029C>T
NM_000257.3:c.5029C>T
NR_126491.1:n.189G>A

Protein change:

R1677C

Links:

dbSNP: rs377461670

NCBI 1000 Genomes Browser:

rs377461670

Molecular consequence:

NM_000257.4:c.5029C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_126491.1:n.189G>A - 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
SCV002641797	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 27, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21750094, 27532257, 29773157, 30924982 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002641797

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 27, 2022)

germline

clinical testing

PubMed (4)
[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

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002641797.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The p.R1677C variant (also known as c.5029C>T), located in coding exon 33 of the MYH7 gene, results from a C to T substitution at nucleotide position 5029. The arginine at codon 1677 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was detected in a patient referred for hypertrophic cardiomyopathy genetic testing; however, clinical details were limited (Walsh R et al. Genet Med. 2017;19:192-203). This variant has also been reported in a dilated cardiomyopathy (DCM) cohort (Ware JS et al. J Am Coll Cardiol, 2018 05;71:2293-2302). This alteration was also detected in siblings with left ventricular non-compaction (LVNC) who also carried a nonsense alteration in MYH7 (Kolokotronis K et al. Hum Mutat, 2019 08;40:1101-1114). Another variant affecting this codon (p.R1677H) has been reported in cardiomyopathy cohorts; however clinical details are limited (Waldmüller S et al. Eur J Heart Fail. 2011;13:1185-92). 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: Sep 29, 2024

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