ClinVar Miner

Submissions for variant NM_001145809.2(MYH14):c.1382G>A (p.Arg461His)

dbSNP: rs370353590
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000037024 SCV000060680 uncertain significance not specified 2016-12-13 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Arg461His var iant in MYH14 has been identified by our laboratory in 2 individuals with modera te sensorineural hearing loss, but it did not segregate with hearing loss in an affected family member. This variant has also been identified in 2/7738 East Asi an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs370353590); however its frequency is not high enough to rule o ut a pathogenic role. Computational prediction tools and conservation analyses s uggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while the clinical sig nificance of the p.Arg461His variant is uncertain, the nonsegregation event sugg ests that it is more likely to be benign.
GeneDx RCV001770057 SCV001993626 uncertain significance not provided 2024-04-01 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp RCV001770057 SCV003788141 uncertain significance not provided 2024-10-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 453 of the MYH14 protein (p.Arg453His). This variant is present in population databases (rs370353590, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MYH14-related conditions. ClinVar contains an entry for this variant (Variation ID: 44048). 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 MYH14 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001770057 SCV005409972 uncertain significance not provided 2024-05-24 criteria provided, single submitter clinical testing BS2

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