ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.1051C>T (p.Pro351Ser) (rs773929129)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701139 SCV000829923 uncertain significance Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 351 of the MVK protein (p.Pro351Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs773929129, ExAC no frequency). This variant has not been reported in the literature in individuals with MVK-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001002446 SCV001160386 uncertain significance not specified 2019-03-27 criteria provided, single submitter clinical testing The MVK c.1051C>T; p.Pro351Ser variant (rs773929129), to our knowledge, is not reported in the medical literature or gene-specific databases. The variant is reported in the ClinVar database (Variation ID: 578204) and in the general population in 2 out of 248176 in the Genome Aggregation Database, indicating it is not a common polymorphism. The proline at this position is weakly conserved and computational algorithms (PolyPhen-2, SIFT) predict this variant is tolerated. Due to limited information, the clinical significance of the variant is uncertain at this time.

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