NM_000257.4(MYH7):c.3235C>T (p.Arg1079Trp) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 29, 2024
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:: RCV000326571.17

Allele description [Variation Report for NM_000257.4(MYH7):c.3235C>T (p.Arg1079Trp)]

NM_000257.4(MYH7):c.3235C>T (p.Arg1079Trp)

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.3235C>T (p.Arg1079Trp)

HGVS:

NC_000014.9:g.23422190G>A
NG_007884.1:g.18472C>T
NM_000257.4:c.3235C>TMANE SELECT
NP_000248.2:p.Arg1079Trp
LRG_384t1:c.3235C>T
LRG_384:g.18472C>T
NC_000014.8:g.23891399G>A
NM_000257.2:c.3235C>T
NM_000257.3:c.3235C>T

Protein change:

R1079W

Links:

dbSNP: rs192722540

NCBI 1000 Genomes Browser:

rs192722540

Molecular consequence:

NM_000257.4:c.3235C>T - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000623692	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 29, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27930701, 28704380, 33996946, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000623692

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 29, 2024)

germline

clinical testing

PubMed (4)
[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

Natural and Undetermined Sudden Death: Value of Post-Mortem Genetic Investigation.

Sanchez O, Campuzano O, Fernández-Falgueras A, Sarquella-Brugada G, Cesar S, Mademont I, Mates J, Pérez-Serra A, Coll M, Pico F, Iglesias A, Tirón C, Allegue C, Carro E, Gallego MÁ, Ferrer-Costa C, Hospital A, Bardalet N, Borondo JC, Vingut A, Arbelo E, Brugada J, et al.

PLoS One. 2016;11(12):e0167358. doi: 10.1371/journal.pone.0167358. Erratum in: PLoS One. 2017 Feb 6;12(2):e0171893. doi: 10.1371/journal.pone.0171893..

PubMed [citation]

PMID:: 27930701
PMCID:: PMC5145162

Molecular investigation by whole exome sequencing revealed a high proportion of pathogenic variants among Thai victims of sudden unexpected death syndrome.

Suktitipat B, Sathirareuangchai S, Roothumnong E, Thongnoppakhun W, Wangkiratikant P, Vorasan N, Krittayaphong R, Pithukpakorn M, Boonyapisit W.

PLoS One. 2017;12(7):e0180056. doi: 10.1371/journal.pone.0180056.

PubMed [citation]

PMID:: 28704380
PMCID:: PMC5509116

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000623692.7

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

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1079 of the MYH7 protein (p.Arg1079Trp). This variant is present in population databases (rs192722540, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of MYH7-related conditions (PMID: 27930701, 28704380, 33996946). ClinVar contains an entry for this variant (Variation ID: 164304). 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 with a positive predictive value of 95%. 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.

#	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 16, 2025

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