ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.409G>A (p.Glu137Lys)

gnomAD frequency: 0.00002  dbSNP: rs752658033
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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 RCV001981970 SCV002217293 uncertain significance Hypertrophic cardiomyopathy 14 2024-09-06 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 137 of the MYH6 protein (p.Glu137Lys). This variant is present in population databases (rs752658033, 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: 1432256). 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 not expected to disrupt MYH6 protein function with a negative 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 RCV002324358 SCV002632364 uncertain significance Cardiovascular phenotype 2024-04-11 criteria provided, single submitter clinical testing The p.E137K variant (also known as c.409G>A), located in coding exon 3 of the MYH6 gene, results from a G to A substitution at nucleotide position 409. The glutamic acid at codon 137 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Lopes LR et al. Heart, 2015 Feb;101:294-301). This amino acid position is well 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 RCV002484637 SCV002785145 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-08-12 criteria provided, single submitter clinical testing
GeneDx RCV003320857 SCV004025801 uncertain significance not provided 2023-02-09 criteria provided, single submitter clinical testing Identified in at least one patient with HCM in published literature (Lopes et al., 2015); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25351510)

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