NM_000257.4(MYH7):c.4402G>A (p.Glu1468Lys) AND Hypertrophic cardiomyopathy

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 27, 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:: RCV000689327.7

Allele description

NM_000257.4(MYH7):c.4402G>A (p.Glu1468Lys)

Genes:

MYH7:myosin heavy chain 7 [Gene - OMIM - HGNC]
MHRT:myosin heavy chain associated RNA transcript [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_000257.4(MYH7):c.4402G>A (p.Glu1468Lys)

HGVS:

NC_000014.9:g.23417270C>T
NG_007884.1:g.23392G>A
NM_000257.4:c.4402G>AMANE SELECT
NP_000248.2:p.Glu1468Lys
LRG_384t1:c.4402G>A
LRG_384:g.23392G>A
NC_000014.8:g.23886479C>T
NM_000257.2:c.4402G>A
NM_000257.3:c.4402G>A
NR_126491.1:n.710C>T

Protein change:

E1468K

Links:

dbSNP: rs876657884

NCBI 1000 Genomes Browser:

rs876657884

Molecular consequence:

NM_000257.4:c.4402G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_126491.1:n.710C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV000816972	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 27, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 26656175, 27247418, 27737317, 30297972, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000816972

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 27, 2023)

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

Molecular analysis of sarcomeric and non-sarcomeric genes in patients with hypertrophic cardiomyopathy.

Bottillo I, D'Angelantonio D, Caputo V, Paiardini A, Lipari M, De Bernardo C, Giannarelli D, Pizzuti A, Majore S, Castori M, Zachara E, Re F, Grammatico P.

Gene. 2016 Feb 15;577(2):227-35. doi: 10.1016/j.gene.2015.11.048. Epub 2015 Dec 2.

PubMed [citation]

PMID:: 26656175

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 Invitae, SCV000816972.7

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

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1468 of the MYH7 protein (p.Glu1468Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 26656175, 27247418, 27737317, 30297972; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 235033). 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%. For these reasons, this variant has been classified as Pathogenic.

#	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 7, 2024

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