ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.3455A>T (p.Glu1152Val)

gnomAD frequency: 0.00001  dbSNP: rs397516184
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035854 SCV000059505 uncertain significance not specified 2014-08-07 criteria provided, single submitter clinical testing The Glu1152Val variant in MYH7 has been identified by our laboratory as homozygo us in 1 Caucasian adult with DCM as well as heterozygous in 1 sibling with borde rline left ventricular hypertrophy (Pugh 2014). Data from large population studi es is insufficient to assess the frequency of this variant. Glutamic acid (Glu) at position 1152 is highly conserved in mammals and across evolutionarily distan t species and the change to valine (Val) was predicted to be pathogenic using a computational tool clinically validated by our laboratory. This tool's pathogeni c prediction is estimated to be correct 94% of the time (Jordan 2011). In summar y, the clinical significance of the Glu1152Val variant is uncertain.
Invitae RCV000706291 SCV000835331 uncertain significance Hypertrophic cardiomyopathy 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1152 of the MYH7 protein (p.Glu1152Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 24503780). ClinVar contains an entry for this variant (Variation ID: 42961). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769451 SCV000900844 uncertain significance Cardiomyopathy 2022-06-02 criteria provided, single submitter clinical testing
GeneDx RCV002259311 SCV002538767 uncertain significance not provided 2022-06-08 criteria provided, single submitter clinical testing Reported in the apparent homozygous state in a patient with a personal and family history of dilated cardiomyopathy, but familial segregation information was not provided (Pugh et al., 2014); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27532257, 24503780)
Ambry Genetics RCV002453300 SCV002616771 uncertain significance Cardiovascular phenotype 2021-12-17 criteria provided, single submitter clinical testing The p.E1152V variant (also known as c.3455A>T), located in coding exon 25 of the MYH7 gene, results from an A to T substitution at nucleotide position 3455. The glutamic acid at codon 1152 is replaced by valine, an amino acid with dissimilar properties. This alteration has been reported in a cardiomyopathy cohort and a genetic testing cohort; however, clinical details were limited (Homburger JR et al. Proc Natl Acad Sci U S A, 2016 06;113:6701-6; Walsh R et al. Genet Med, 2017 02;19:192-203). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002477071 SCV002777261 uncertain significance Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy 2021-08-02 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV002259311 SCV004236703 uncertain significance not provided 2023-02-09 criteria provided, single submitter clinical testing

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