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NM_000257.4(MYH7):c.4717G>A (p.Glu1573Lys) AND Cardiomyopathy

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Nov 2, 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:
RCV001183228.8

Allele description [Variation Report for NM_000257.4(MYH7):c.4717G>A (p.Glu1573Lys)]

NM_000257.4(MYH7):c.4717G>A (p.Glu1573Lys)

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.4717G>A (p.Glu1573Lys)
HGVS:
  • NC_000014.9:g.23416240C>T
  • NG_007884.1:g.24422G>A
  • NM_000257.4:c.4717G>AMANE SELECT
  • NP_000248.2:p.Glu1573Lys
  • LRG_384t1:c.4717G>A
  • LRG_384:g.24422G>A
  • NC_000014.8:g.23885449C>T
  • NM_000257.2:c.4717G>A
  • NM_000257.3:c.4717G>A
  • NR_126491.1:n.501C>T
  • P12883:p.Glu1573Lys
Protein change:
E1573K
Links:
UniProtKB: P12883#VAR_073884; dbSNP: rs750987717
NCBI 1000 Genomes Browser:
rs750987717
Molecular consequence:
  • NM_000257.4:c.4717G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_126491.1:n.501C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
8

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
SCV001348906Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Dec 9, 2022) 		germlineclinical testing

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

SCV004814373All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Nov 2, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown8not providednot provided108544not providedclinical testing

Citations

PubMed

Mutations in the sarcomere gene MYH7 in Ebstein anomaly.

Postma AV, van Engelen K, van de Meerakker J, Rahman T, Probst S, Baars MJ, Bauer U, Pickardt T, Sperling SR, Berger F, Moorman AF, Mulder BJ, Thierfelder L, Keavney B, Goodship J, Klaassen S.

Circ Cardiovasc Genet. 2011 Feb;4(1):43-50. doi: 10.1161/CIRCGENETICS.110.957985. Epub 2010 Dec 2.

PubMed [citation]
PMID:
21127202

Novel Genetic Triggers and Genotype-Phenotype Correlations in Patients With Left Ventricular Noncompaction.

Miszalski-Jamka K, Jefferies JL, Mazur W, Głowacki J, Hu J, Lazar M, Gibbs RA, Liczko J, Kłyś J, Venner E, Muzny DM, Rycaj J, Białkowski J, Kluczewska E, Kalarus Z, Jhangiani S, Al-Khalidi H, Kukulski T, Lupski JR, Craigen WJ, Bainbridge MN.

Circ Cardiovasc Genet. 2017 Aug;10(4). doi:pii: e001763. 10.1161/CIRCGENETICS.117.001763.

PubMed [citation]
PMID:
28798025
PMCID:
PMC5665372
See all PubMed Citations (4)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001348906.3

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

Description

This missense variant replaces glutamic acid with lysine at codon 1573 of the MYH7 protein. Computational prediction suggests that this variant may have 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 an individual affected with left ventricular non-compaction (PMID: 28798025) and in an individual with dilated cardiomyopathy (PMID: 32880476). This variant has also been reported in an individual affected with Ebstein anomaly and perimembranous ventricular septal defect, as well as in the unaffected father (PMID: 21127202). This variant has been identified in 15/251370 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 All of Us Research Program, National Institutes of Health, SCV004814373.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided8not providednot providedclinical testing PubMed (4)

Description

This missense variant replaces glutamic acid with lysine at codon 1573 of the MYH7 protein. Computational prediction suggests that this variant may have 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 an individual affected with left ventricular non-compaction (PMID: 28798025) and in an individual with dilated cardiomyopathy (PMID: 32880476). This variant has also been reported in an individual affected with Ebstein anomaly and perimembranous ventricular septal defect, as well as in the unaffected father (PMID: 21127202). This variant has been identified in 15/251370 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 provided8not providednot providednot provided

Last Updated: Nov 10, 2024