ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4747G>A (p.Glu1583Lys)

gnomAD frequency: 0.00006  dbSNP: rs397516771
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Total submissions: 5
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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 RCV000037513 SCV000061171 uncertain significance not specified 2012-03-16 criteria provided, single submitter clinical testing The Glu1583Lys variant in MYH6 has not been reported in the literature nor previ ously identified by our laboratory. Glutamic acid at position 1583 is conserved in evolution, suggesting that a change would impact the protein and computationa l predictions (AlignGVGD, PolyPhen2, and SIFT) also favor a deleterious role. H owever, this information is not predictive enough to assume pathogenicity. Addit ional information is needed to fully assess the clinical significance of the Glu 1583Lys variant.
Ambry Genetics RCV000618656 SCV000740193 uncertain significance Cardiovascular phenotype 2020-12-02 criteria provided, single submitter clinical testing The p.E1583K variant (also known as c.4747G>A), located in coding exon 31 of the MYH6 gene, results from a G to A substitution at nucleotide position 4747. The glutamic acid at codon 1583 is replaced by lysine, an amino acid with similar properties. 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.
GeneDx RCV001550574 SCV001770916 uncertain significance not provided 2024-03-04 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp RCV001852777 SCV002288232 uncertain significance Hypertrophic cardiomyopathy 14 2024-08-13 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1583 of the MYH6 protein (p.Glu1583Lys). This variant is present in population databases (rs397516771, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 44518). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH6 protein function with a positive predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV002490511 SCV002781977 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-07-23 criteria provided, single submitter clinical testing

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