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NM_000257.4(MYH7):c.4498C>T (p.Arg1500Trp) AND Cardiomyopathy

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Aug 22, 2022
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:
RCV000770475.3

Allele description [Variation Report for NM_000257.4(MYH7):c.4498C>T (p.Arg1500Trp)]

NM_000257.4(MYH7):c.4498C>T (p.Arg1500Trp)

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.4498C>T (p.Arg1500Trp)
HGVS:
  • NC_000014.9:g.23417174G>A
  • NG_007884.1:g.23488C>T
  • NM_000257.4:c.4498C>TMANE SELECT
  • NP_000248.2:p.Arg1500Trp
  • LRG_384t1:c.4498C>T
  • LRG_384:g.23488C>T
  • NC_000014.8:g.23886383G>A
  • NM_000257.2:c.4498C>T
  • NM_000257.3:c.4498C>T
Protein change:
R1500W
Links:
dbSNP: rs45544633
NCBI 1000 Genomes Browser:
rs45544633
Molecular consequence:
  • NM_000257.4:c.4498C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000901918CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Jun 12, 2017)
germlineclinical testing

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

SCV004359533Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Aug 22, 2022)
germlineclinical testing

PubMed (12)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

[Changes in the specificity of DNA methylation in cattle blood lymphocytes under chronic lymphoid leukemia].

Burtseva NN, Demidkina NP, Azizov IuM, Vaniushin BF.

Biokhimiia. 1978 Nov;43(11):2082-91. Russian.

PubMed [citation]
PMID:
737223

Spectroscopic studies on the interaction of Au(III) with nucleosides, nucleotides, and dimethyl phosphate.

Chatterji D, Nandi US, Podder SK.

Biopolymers. 1977 Sep;16(9):1863-78. No abstract available.

PubMed [citation]
PMID:
901918
See all PubMed Citations (12)

Details of each submission

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository, SCV000901918.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Color Diagnostics, LLC DBA Color Health, SCV004359533.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (12)

Description

This missense variant replaces arginine with tryptophan at codon 1500 in the LMM domain in the C-terminal tail region of the MYH7 protein that forms the thick filament backbone and interacts with other proteins. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). In vitro functional studies provide some evidence that this variant may destabilize the MYH7 protein (PMID: 19854198, 22155079, 24047955). This variant has been reported in more than 10 individuals affected with dilated cardiomyopathy (PMID: 15556047, 18660445, 24119082, 26383716, 28750076, 31317183; communication with external laboratories: ClinVar SCV000901918.1 and SCV000737223.3) and in multiple individuals with left ventricular noncompaction cardiomyopathy (communication with external laboratories: ClinVar SCV000199112.4 and SCV000737223.3). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024