NM_000257.4(MYH7):c.3667G>A (p.Glu1223Lys) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 17, 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:: RCV002517699.3

Allele description [Variation Report for NM_000257.4(MYH7):c.3667G>A (p.Glu1223Lys)]

NM_000257.4(MYH7):c.3667G>A (p.Glu1223Lys)

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.3667G>A (p.Glu1223Lys)

HGVS:

NC_000014.9:g.23419904C>T
NG_007884.1:g.20758G>A
NM_000257.4:c.3667G>AMANE SELECT
NP_000248.2:p.Glu1223Lys
LRG_384t1:c.3667G>A
LRG_384:g.20758G>A
NC_000014.8:g.23889113C>T
NM_000257.2:c.3667G>A
NM_000257.3:c.3667G>A

Protein change:

E1223K

Links:

dbSNP: rs794727410

NCBI 1000 Genomes Browser:

rs794727410

Molecular consequence:

NM_000257.4:c.3667G>A - 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
SCV003484101	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 17, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29892087, 31737537, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003484101

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 17, 2023)

germline

clinical testing

PubMed (3)
[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

A gene-centric strategy for identifying disease-causing rare variants in dilated cardiomyopathy.

Horvat C, Johnson R, Lam L, Munro J, Mazzarotto F, Roberts AM, Herman DS, Parfenov M, Haghighi A, McDonough B, DePalma SR, Keogh AM, Macdonald PS, Hayward CS, Roberts A, Barton PJR, Felkin LE, Giannoulatou E, Cook SA, Seidman JG, Seidman CE, Fatkin D.

Genet Med. 2019 Jan;21(1):133-143. doi: 10.1038/s41436-018-0036-2. Epub 2018 Jun 11.

PubMed [citation]

PMID:: 29892087
PMCID:: PMC7336363

Variant panorama in 1,385 index patients and sensitivity of expanded next-generation sequencing panels in arrhythmogenic disorders.

Marschall C, Moscu-Gregor A, Klein HG.

Cardiovasc Diagn Ther. 2019 Oct;9(Suppl 2):S292-S298. doi: 10.21037/cdt.2019.06.06.

PubMed [citation]

PMID:: 31737537
PMCID:: PMC6837920

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003484101.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1223 of the MYH7 protein (p.Glu1223Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 29892087, 31737537). ClinVar contains an entry for this variant (Variation ID: 195928). 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. 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: Aug 4, 2024

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