ClinVar Miner

Submissions for variant NM_001145809.2(MYH14):c.359C>T (p.Ser120Leu)

dbSNP: rs119103281
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481506 SCV000568768 pathogenic not provided 2017-03-27 criteria provided, single submitter clinical testing The S120L variant in the MYH14 gene has been reported to segregate with hearing loss in all affected members of a large German kindred (Yang et al., 2005). The S120L variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The S120L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret S120L as a pathogenic variant.
CeGaT Center for Human Genetics Tuebingen RCV000481506 SCV001500217 pathogenic not provided 2020-12-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003407256 SCV004110208 uncertain significance MYH14-related condition 2023-04-07 criteria provided, single submitter clinical testing The MYH14 c.359C>T variant is predicted to result in the amino acid substitution p.Ser120Leu. This variant was reported to segregate with hearing loss in 10 affected and 14 unaffected individuals across 4 generations in a single family, although information on which individuals were tested for the variant was not provided (Yang et al. 2005. PubMed ID: 16222661). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Invitae RCV000481506 SCV004298435 pathogenic not provided 2023-07-14 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 120 of the MYH14 protein (p.Ser120Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with deafness (PMID: 16222661, 20533261). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2200). 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 MYH14 protein function. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000002284 SCV000022442 pathogenic Autosomal dominant nonsyndromic hearing loss 4A 2005-11-15 no assertion criteria provided literature only

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