ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.2440C>A (p.Leu814Met)

dbSNP: rs150675144
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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 RCV000538124 SCV000648232 uncertain significance Hypertrophic cardiomyopathy 14 2024-10-12 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 814 of the MYH6 protein (p.Leu814Met). This variant is present in population databases (rs150675144, gnomAD 0.006%). This missense change has been observed in individual(s) with Brugada syndrome (PMID: 26220970). ClinVar contains an entry for this variant (Variation ID: 312870). 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 RCV000621625 SCV000740172 uncertain significance Cardiovascular phenotype 2024-03-05 criteria provided, single submitter clinical testing The p.L814M variant (also known as c.2440C>A), located in coding exon 19 of the MYH6 gene, results from a C to A substitution at nucleotide position 2440. The leucine at codon 814 is replaced by methionine, an amino acid with highly similar properties. This variant has been detected in a suspected Brugada syndrome cohort; however, details were not provided (Di Resta C et al. Hum Mol Genet. 2015 Oct;24(20):5828-35). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated 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 RCV002261044 SCV002541602 uncertain significance not provided 2021-07-13 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002494980 SCV002794495 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-09-08 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV002261044 SCV005192261 uncertain significance not provided criteria provided, single submitter not provided

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