NM_000257.4(MYH7):c.541G>A (p.Gly181Arg) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 14, 2023
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:: RCV001207953.6

Allele description [Variation Report for NM_000257.4(MYH7):c.541G>A (p.Gly181Arg)]

NM_000257.4(MYH7):c.541G>A (p.Gly181Arg)

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.541G>A (p.Gly181Arg)

HGVS:

NC_000014.9:g.23431859C>T
NG_007884.1:g.8803G>A
NM_000257.4:c.541G>AMANE SELECT
NP_000248.2:p.Gly181Arg
LRG_384:g.8803G>A
NC_000014.8:g.23901068C>T
NM_000257.2:c.541G>A
NM_000257.3:c.541G>A

Protein change:

G181R

Links:

dbSNP: rs760187215

NCBI 1000 Genomes Browser:

rs760187215

Molecular consequence:

NM_000257.4:c.541G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypertrophic cardiomyopathy
Synonyms:: HYPERTROPHIC MYOCARDIOPATHY
Identifiers:: MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001379321	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 14, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27532257, 34935411, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001379321

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 14, 2023)

germline

clinical testing

PubMed (3)
[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

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

Genotype and Cardiac Outcomes in Pediatric Dilated Cardiomyopathy.

Khan RS, Pahl E, Dellefave-Castillo L, Rychlik K, Ing A, Yap KL, Brew C, Johnston JR, McNally EM, Webster G.

J Am Heart Assoc. 2022 Jan 4;11(1):e022854. doi: 10.1161/JAHA.121.022854. Epub 2021 Dec 22.

PubMed [citation]

PMID:: 34935411
PMCID:: PMC9075202

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001379321.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

ClinVar contains an entry for this variant (Variation ID: 619082). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function. This missense change has been observed in individual(s) with MYH7-related conditions (PMID: 27532257, 34935411). This variant is present in population databases (rs760187215, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 181 of the MYH7 protein (p.Gly181Arg).

#	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

ClinVar

Relating variation to medicine