NM_000257.4(MYH7):c.2846A>T (p.Glu949Val) AND Cardiomyopathy

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Aug 15, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000770486.8

Allele description [Variation Report for NM_000257.4(MYH7):c.2846A>T (p.Glu949Val)]

NM_000257.4(MYH7):c.2846A>T (p.Glu949Val)

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.2846A>T (p.Glu949Val)

Other names:

p.E949V:GAG>GTG

HGVS:

NC_000014.9:g.23423983T>A
NG_007884.1:g.16679A>T
NM_000257.4:c.2846A>TMANE SELECT
NP_000248.2:p.Glu949Val
LRG_384t1:c.2846A>T
LRG_384:g.16679A>T
NC_000014.8:g.23893192T>A
NM_000257.2:c.2846A>T
NM_000257.3:c.2846A>T
c.2846A>T

Protein change:

E949V

Links:

dbSNP: rs397516175

NCBI 1000 Genomes Browser:

rs397516175

Molecular consequence:

NM_000257.4:c.2846A>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000901930	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 22, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001357319	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 25, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25351510, 27247418, 27532257, 25741868
SCV004822511	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Aug 15, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25351510, 27247418, 27532257, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000901930

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 22, 2015)

germline

clinical testing

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

SCV001357319

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 25, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004822511

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Aug 15, 2023)

germline

clinical testing

PubMed (4)
[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	3	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy.

Lopes LR, Syrris P, Guttmann OP, O'Mahony C, Tang HC, Dalageorgou C, Jenkins S, Hubank M, Monserrat L, McKenna WJ, Plagnol V, Elliott PM.

Heart. 2015 Feb;101(4):294-301. doi: 10.1136/heartjnl-2014-306387. Epub 2014 Oct 28.

PubMed [citation]

PMID:: 25351510
PMCID:: PMC4345808

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 (4)

Details of each submission

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository, SCV000901930.1

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

#	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

From Color Diagnostics, LLC DBA Color Health, SCV001357319.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This missense variant replaces glutamic acid with valine at codon 949 of the MYH7 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 25351510, 27247418, 27532257). This variant has been identified in 2/251494 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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

From All of Us Research Program, National Institutes of Health, SCV004822511.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (4)

Description

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		3	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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