ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.5656G>A (p.Glu1886Lys)

gnomAD frequency: 0.00006  dbSNP: rs138864419
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000795486 SCV000934950 uncertain significance Hypertrophic cardiomyopathy 14 2024-11-24 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 1886 of the MYH6 protein (p.Glu1886Lys). This variant is present in population databases (rs138864419, gnomAD 0.02%). 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: 642093). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MYH6 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects MYH6 function (PMID: 19336582). 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.
Ambry Genetics RCV002345753 SCV002652979 uncertain significance Cardiovascular phenotype 2024-11-03 criteria provided, single submitter clinical testing The p.E1886K variant (also known as c.5656G>A), located in coding exon 35 of the MYH6 gene, results from a G to A substitution at nucleotide position 5656. The glutamic acid at codon 1886 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic RCV003480827 SCV004226492 uncertain significance not provided 2022-06-30 criteria provided, single submitter clinical testing PP3
Fulgent Genetics, Fulgent Genetics RCV005012320 SCV005636739 uncertain significance Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2024-04-11 criteria provided, single submitter clinical testing

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