ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4918G>A (p.Glu1640Lys)

gnomAD frequency: 0.00002  dbSNP: rs748924413
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208194 SCV000264072 uncertain significance Primary familial hypertrophic cardiomyopathy 2015-06-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000816132 SCV000956625 uncertain significance Hypertrophic cardiomyopathy 14 2024-09-22 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 1640 of the MYH6 protein (p.Glu1640Lys). This variant is present in population databases (rs748924413, gnomAD 0.01%). This missense change has been observed in individual(s) with unspecified cardiomyopathy (PMID: 30847666). ClinVar contains an entry for this variant (Variation ID: 222717). 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%. 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 RCV002347813 SCV002645440 uncertain significance Cardiovascular phenotype 2023-12-01 criteria provided, single submitter clinical testing The p.E1640K variant (also known as c.4918G>A), located in coding exon 31 of the MYH6 gene, results from a G to A substitution at nucleotide position 4918. The glutamic acid at codon 1640 is replaced by lysine, an amino acid with similar properties. This variant was detected in a cardiomyopathy genetic testing cohort; however, clinical details were limited (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). 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.
Fulgent Genetics, Fulgent Genetics RCV002485362 SCV002785160 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2022-04-29 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003129809 SCV003809563 uncertain significance not provided 2023-01-25 criteria provided, single submitter clinical testing

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