NM_000257.4(MYH7):c.872C>T (p.Ser291Phe) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 17, 2020
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:: RCV001349519.7

Allele description [Variation Report for NM_000257.4(MYH7):c.872C>T (p.Ser291Phe)]

NM_000257.4(MYH7):c.872C>T (p.Ser291Phe)

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.872C>T (p.Ser291Phe)

HGVS:

NC_000014.9:g.23430924G>A
NG_007884.1:g.9738C>T
NM_000257.4:c.872C>TMANE SELECT
NP_000248.2:p.Ser291Phe
LRG_384t1:c.872C>T
LRG_384:g.9738C>T
NC_000014.8:g.23900133G>A
NM_000257.2:c.872C>T
c.872C>T

Protein change:

S291F

Links:

dbSNP: rs397516272

NCBI 1000 Genomes Browser:

rs397516272

Molecular consequence:

NM_000257.4:c.872C>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
SCV001543870	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 17, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 21943931, 27247418, 24093860, 27532257, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001543870

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 17, 2020)

germline

clinical testing

PubMed (5)
[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

Electrocardiographic features of sarcomere mutation carriers with and without clinically overt hypertrophic cardiomyopathy.

Lakdawala NK, Thune JJ, Maron BJ, Cirino AL, Havndrup O, Bundgaard H, Christiansen M, Carlsen CM, Dorval JF, Kwong RY, Colan SD, Køber LV, Ho CY.

Am J Cardiol. 2011 Dec 1;108(11):1606-13. doi: 10.1016/j.amjcard.2011.07.019. Epub 2011 Sep 21.

PubMed [citation]

PMID:: 21943931
PMCID:: PMC3215918

Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation.

Homburger JR, Green EM, Caleshu C, Sunitha MS, Taylor RE, Ruppel KM, Metpally RP, Colan SD, Michels M, Day SM, Olivotto I, Bustamante CD, Dewey FE, Ho CY, Spudich JA, Ashley EA.

Proc Natl Acad Sci U S A. 2016 Jun 14;113(24):6701-6. doi: 10.1073/pnas.1606950113. Epub 2016 May 31.

PubMed [citation]

PMID:: 27247418
PMCID:: PMC4914177

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001543870.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with phenylalanine at codon 291 of the MYH7 protein (p.Ser291Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 21943931, 27247418, 24093860). ClinVar contains an entry for this variant (Variation ID: 43110). 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 is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15").

#	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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