ClinVar Miner

Submissions for variant NM_001145809.2(MYH14):c.1655C>T (p.Pro552Leu)

gnomAD frequency: 0.00003  dbSNP: rs727505282
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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 RCV000156811 SCV000206532 uncertain significance not specified 2014-10-02 criteria provided, single submitter clinical testing The Pro552Leu variant in MYH14 gene has not been previously reported in individu als with hearing loss and was absent from large population studies. Computationa l prediction tools and conservation analysis suggest that this variant may impac t the protein; though this information is not predictive enough to determine pat hogenicity. The variant is located in the last three bases of the exon, which is part of the 5? splice region. Computational tools do not suggest an impact to s plicing; however, this data is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the Pro552Leu variant is uncertain.
CeGaT Center for Human Genetics Tuebingen RCV001815213 SCV002063807 uncertain significance not provided 2021-10-01 criteria provided, single submitter clinical testing
GeneDx RCV001815213 SCV002098255 uncertain significance not provided 2022-02-15 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001815213 SCV002274679 uncertain significance not provided 2021-08-23 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 544 of the MYH14 protein (p.Pro544Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs727505282, ExAC 0.01%). This missense change has been observed in individual(s) with clinical features of MYH14-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 180008). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.

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