ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.5137G>A (p.Glu1713Lys)

gnomAD frequency: 0.00003  dbSNP: rs369275573
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000250543 SCV000318049 uncertain significance Cardiovascular phenotype 2023-04-19 criteria provided, single submitter clinical testing The p.E1713K variant (also known as c.5137G>A), located in coding exon 32 of the MYH6 gene, results from a G to A substitution at nucleotide position 5137. The glutamic acid at codon 1713 is replaced by lysine, an amino acid with similar properties. This variant has been detected in an individual from a left ventricular non-compaction cohort (Hirono K et al. J Clin Med, 2020 Mar;9). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000465457 SCV000546156 uncertain significance Hypertrophic cardiomyopathy 14 2023-12-28 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 1713 of the MYH6 protein (p.Glu1713Lys). This variant is present in population databases (rs369275573, gnomAD 0.02%). This missense change has been observed in individual(s) with left ventricular noncompaction (PMID: 32183154). ClinVar contains an entry for this variant (Variation ID: 263451). 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 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.
GeneDx RCV000520603 SCV000618856 uncertain significance not provided 2023-12-15 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35621855, 32183154, 33309763)

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