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NM_000257.4(MYH7):c.4772T>A (p.Leu1591Gln) AND Cardiomyopathy

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
Jan 11, 2024
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:
RCV000778015.9

Allele description [Variation Report for NM_000257.4(MYH7):c.4772T>A (p.Leu1591Gln)]

NM_000257.4(MYH7):c.4772T>A (p.Leu1591Gln)

Genes:
LOC126861897:BRD4-independent group 4 enhancer GRCh37_chr14:23884455-23885654 [Gene]
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.4772T>A (p.Leu1591Gln)
HGVS:
  • NC_000014.9:g.23416185A>T
  • NG_007884.1:g.24477T>A
  • NM_000257.4:c.4772T>AMANE SELECT
  • NP_000248.2:p.Leu1591Gln
  • LRG_384t1:c.4772T>A
  • LRG_384:g.24477T>A
  • NC_000014.8:g.23885394A>T
  • NM_000257.2:c.4772T>A
  • NM_000257.3:c.4772T>A
  • NR_126491.1:n.446A>T
Protein change:
L1591Q
Links:
dbSNP: rs730880808
NCBI 1000 Genomes Browser:
rs730880808
Molecular consequence:
  • NM_000257.4:c.4772T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_126491.1:n.446A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
13

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000914125Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Nov 21, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002042687CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Dec 21, 2020) 		germlineclinical testing

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

SCV004814371All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Jan 11, 2024) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown13not providednot provided108544not providedclinical testing

Citations

PubMed

Post-mortem genetic analysis in juvenile cases of sudden cardiac death.

Campuzano O, Sanchez-Molero O, Allegue C, Coll M, Mademont-Soler I, Selga E, Ferrer-Costa C, Mates J, Iglesias A, Sarquella-Brugada G, Cesar S, Brugada J, Castellà J, Medallo J, Brugada R.

Forensic Sci Int. 2014 Dec;245:30-7. doi: 10.1016/j.forsciint.2014.10.004. Epub 2014 Oct 14.

PubMed [citation]
PMID:
25447171

Personalized Interpretation and Clinical Translation of Genetic Variants Associated With Cardiomyopathies.

Campuzano O, Fernandez-Falgueras A, Sarquella-Brugada G, Cesar S, Arbelo E, García-Álvarez A, Jordà P, Coll M, Fiol V, Iglesias A, Perez-Serra A, Mates J, Del Olmo B, Ferrer C, Alcalde M, Puigmulé M, Mademont-Soler I, Pico F, Lopez L, Tiron C, Brugada J, Brugada R.

Front Genet. 2019;10:450. doi: 10.3389/fgene.2019.00450.

PubMed [citation]
PMID:
31156706
PMCID:
PMC6529573
See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000914125.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This missense variant replaces leucine with glutamine at codon 1591 of the MYH7 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with sudden cardiac death and myocarditis (PMID 25447171). This individual and six relatives diagnosed with arrhythmogenic cardiomyopathy all carried a pathogenic truncation variant in the PKP2 gene that could explain the observed phenotype in this family (PMID: 31156706). This variant has been identified in 10/251476 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.

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

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV002042687.1

#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 All of Us Research Program, National Institutes of Health, SCV004814371.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided13not providednot providedclinical testing PubMed (2)

Description

This missense variant replaces leucine with glutamine at codon 1591 of the MYH7 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with sudden cardiac death and myocarditis (PMID 25447171). This individual and six relatives diagnosed with arrhythmogenic cardiomyopathy all carried a pathogenic truncation variant in the PKP2 gene that could explain the observed phenotype in this family (PMID: 31156706). This variant has been identified in 10/251476 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided13not providednot providednot provided

Last Updated: Jul 29, 2024