ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.190G>A (p.Glu64Lys)

gnomAD frequency: 0.00005  dbSNP: rs750818212
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001201962 SCV001373057 uncertain significance Hypertrophic cardiomyopathy 14 2023-11-13 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 64 of the MYH6 protein (p.Glu64Lys). This variant is present in population databases (rs750818212, gnomAD 0.006%). 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: 933695). 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.
GeneDx RCV002269343 SCV002552780 uncertain significance not provided 2022-07-08 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002411736 SCV002717932 uncertain significance Cardiovascular phenotype 2022-10-03 criteria provided, single submitter clinical testing The p.E64K variant (also known as c.190G>A), located in coding exon 1 of the MYH6 gene, results from a G to A substitution at nucleotide position 190. The glutamic acid at codon 64 is replaced by lysine, an amino acid with similar properties. This variant was detected on exome sequencing in a patient with normal echocardiogram who had short stature, brachydactyly, intellectual developmental disability and seizures syndrome who was homozygous for a nonsense variant the PRMT7 gene (Agolini E et al. Clin. Genet., 2018 03;93:675-681). 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 RCV002484080 SCV002786035 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-09-10 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV002269343 SCV004226496 uncertain significance not provided 2022-10-12 criteria provided, single submitter clinical testing

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