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NM_000257.4(MYH7):c.2845G>A (p.Glu949Lys) AND Primary dilated cardiomyopathy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 11, 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:
RCV003996097.2

Allele description [Variation Report for NM_000257.4(MYH7):c.2845G>A (p.Glu949Lys)]

NM_000257.4(MYH7):c.2845G>A (p.Glu949Lys)

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.2845G>A (p.Glu949Lys)
Other names:
NM_000257.4(MYH7):c.2845G>A
HGVS:
  • NC_000014.9:g.23423984C>T
  • NG_007884.1:g.16678G>A
  • NM_000257.4:c.2845G>AMANE SELECT
  • NP_000248.2:p.Glu949Lys
  • LRG_384t1:c.2845G>A
  • LRG_384:g.16678G>A
  • NC_000014.8:g.23893193C>T
  • NM_000257.2:c.2845G>A
  • P12883:p.Glu949Lys
Protein change:
E949K; GLU949LYS
Links:
UniProtKB: P12883#VAR_004598; OMIM: 160760.0007; dbSNP: rs121913629
NCBI 1000 Genomes Browser:
rs121913629
Molecular consequence:
  • NM_000257.4:c.2845G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Primary dilated cardiomyopathy (DCM)
Synonyms:
Dilated Cardiomyopathy
Identifiers:
EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004840111All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely Pathogenic
(Dec 11, 2023)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not providedclinical testing

Citations

PubMed

Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy.

Watkins H, Rosenzweig A, Hwang DS, Levi T, McKenna W, Seidman CE, Seidman JG.

N Engl J Med. 1992 Apr 23;326(17):1108-14.

PubMed [citation]
PMID:
1552912

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]
PMID:
27532257
PMCID:
PMC5116235
See all PubMed Citations (4)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004840111.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (4)

Description

The c.2845G>A (p.Glu949Lys) variant in MYH7 gene, that encodes for myosin heavy chain 7, has been identified in at least twelve individuals affected with Hypertrophic Cardiomyopathy (HCM) (ClinGen Expert Panel review [ClinVar ID: 14093], PMID:1552912, 27532257, 28815794, 1552912). This variant has been reported as de novo status in a proband with restrictive cardiomyopathy (ClinVar ID: 14093, PMID: NA). In-silico computational prediction tools suggest that this variant may have deleterious effect on the protein function (REVEL score: 0.909). This variant is found to be absent in the general population database (gnomAD) and interpreted as likely pathogenic by the ClinGen Cardiomyopathy Variant Curation Expert Panel (ClinVar ID: 14093). Therefore, the c.2845G>A (p.Glu949Lys) variant in the MYH7 gene is classified as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided1not providednot providednot provided

Last Updated: Jul 15, 2024