NM_000257.4(MYH7):c.4381G>A (p.Glu1461Lys) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 23, 2022
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:: RCV001974183.6

Allele description [Variation Report for NM_000257.4(MYH7):c.4381G>A (p.Glu1461Lys)]

NM_000257.4(MYH7):c.4381G>A (p.Glu1461Lys)

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.4381G>A (p.Glu1461Lys)

HGVS:

NC_000014.9:g.23417291C>T
NG_007884.1:g.23371G>A
NM_000257.4:c.4381G>AMANE SELECT
NP_000248.2:p.Glu1461Lys
LRG_384:g.23371G>A
NC_000014.8:g.23886500C>T
NR_126491.1:n.731C>T

Protein change:

E1461K

Links:

dbSNP: rs2138645640

NCBI 1000 Genomes Browser:

rs2138645640

Molecular consequence:

NM_000257.4:c.4381G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_126491.1:n.731C>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

Recent activity

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Nocardioides sp. zg-1228 Scaffold9_1, whole genome shotgun sequence
Nocardioides sp. zg-1228 Scaffold9_1, whole genome shotgun sequence
gi|1895635003|ref|NZ_JACMYB01000000 gnl|WGS:NZ_JACMYB01|Scaffold9_1

Nucleotide
MULTISPECIES: chaperonin GroEL [Klebsiella]
MULTISPECIES: chaperonin GroEL [Klebsiella]
gi|496082711|ref|WP_008807218.1|

Protein
MULTISPECIES: DUF1176 domain-containing protein [Klebsiella]
MULTISPECIES: DUF1176 domain-containing protein [Klebsiella]
gi|496082718|ref|WP_008807225.1|

Protein
glucose-induced degradation protein 8 homolog [Mus musculus]
glucose-induced degradation protein 8 homolog [Mus musculus]
gi|58037443|ref|NP_083883.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002261979	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 23, 2022)	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

SCV002261979

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 23, 2022)

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, SCV002261979.3

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

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. 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 C0"). 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 glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1461 of the MYH7 protein (p.Glu1461Lys).

#	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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