NM_000257.4(MYH7):c.193T>C (p.Tyr65His) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 8, 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:: RCV003772223.2

Allele description [Variation Report for NM_000257.4(MYH7):c.193T>C (p.Tyr65His)]

NM_000257.4(MYH7):c.193T>C (p.Tyr65His)

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.193T>C (p.Tyr65His)

HGVS:

NC_000014.9:g.23433540A>G
NG_007884.1:g.7122T>C
NM_000257.4:c.193T>CMANE SELECT
NP_000248.2:p.Tyr65His
LRG_384:g.7122T>C
NC_000014.8:g.23902749A>G
NM_000257.3:c.193T>C

Protein change:

Y65H

Links:

dbSNP: rs2138686468

NCBI 1000 Genomes Browser:

rs2138686468

Molecular consequence:

NM_000257.4:c.193T>C - 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

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golgin subfamily A member 6-like protein 24, partial [Danio rerio]
golgin subfamily A member 6-like protein 24, partial [Danio rerio]
gi|2800568279|ref|XP_021324213.2|

Protein
golgin subfamily A member 6-like protein 25 [Danio rerio]
golgin subfamily A member 6-like protein 25 [Danio rerio]
gi|2800568285|ref|XP_068071828.1|

Protein
PREDICTED: Homo sapiens non-compact myelin associated protein (NCMAP), transcrip...
PREDICTED: Homo sapiens non-compact myelin associated protein (NCMAP), transcript variant X1, mRNA
gi|2217267401|ref|XM_011541463.3|

Nucleotide
sigma-54 dependent transcriptional regulator [Pseudomonas protegens]
sigma-54 dependent transcriptional regulator [Pseudomonas protegens]
gi|505447529|ref|WP_015634631.1|

Protein
PREDICTED: Benincasa hispida single-stranded DNA-binding protein, mitochondrial-...
PREDICTED: Benincasa hispida single-stranded DNA-binding protein, mitochondrial-like (LOC120083794), transcript variant X1, mRNA
gi|1955875335|ref|XM_039039670.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004659830	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 8, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004659830

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 8, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004659830.1

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

Description

This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 65 of the MYH7 protein (p.Tyr65His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 1331750). 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 not expected to disrupt MYH7 protein function. 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: Sep 29, 2024

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