NM_000257.4(MYH7):c.2713T>G (p.Cys905Gly) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 19, 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:: RCV003587582.1

Allele description [Variation Report for NM_000257.4(MYH7):c.2713T>G (p.Cys905Gly)]

NM_000257.4(MYH7):c.2713T>G (p.Cys905Gly)

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.2713T>G (p.Cys905Gly)

HGVS:

NC_000014.9:g.23424116A>C
NG_007884.1:g.16546T>G
NM_000257.4:c.2713T>GMANE SELECT
NM_001407004.1:c.2713T>G
NP_000248.2:p.Cys905Gly
NP_000248.2:p.Cys905Gly
NP_001393933.1:p.Cys905Gly
LRG_384t1:c.2713T>G
LRG_384:g.16546T>G
LRG_384p1:p.Cys905Gly
NC_000014.8:g.23893325A>C
NM_000257.2:c.2713T>G

Protein change:

C905G

Molecular consequence:

NM_000257.4:c.2713T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407004.1:c.2713T>G - 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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LOC116134794 [Pistacia vera]
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Gene ID:116134794

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004306094	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 19, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25132132, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004306094

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 19, 2023)

germline

clinical testing

PubMed (2)
[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

Malignant effects of multiple rare variants in sarcomere genes on the prognosis of patients with hypertrophic cardiomyopathy.

Wang J, Wang Y, Zou Y, Sun K, Wang Z, Ding H, Yuan J, Wei W, Hou Q, Wang H, Liu X, Zhang H, Ji Y, Zhou X, Sharma RK, Wang D, Ahmad F, Hui R, Song L.

Eur J Heart Fail. 2014 Sep;16(9):950-7. doi: 10.1002/ejhf.144. Epub 2014 Jul 31.

PubMed [citation]

PMID:: 25132132

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004306094.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. This variant disrupts the p.Cys905 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25132132; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 905 of the MYH7 protein (p.Cys905Gly).

#	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: Feb 20, 2024

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