ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.494C>T (p.Pro165Leu) (rs121917790)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001219913 SCV001391878 likely pathogenic Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2019-04-19 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 165 of the MVK protein (p.Pro165Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with clinical features consistent with hyper IgD syndrome or mevalonate kinase deficiency (PMID: 10369262, 29047407). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 11933). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this allele has been classified as Likely Pathogenic.
OMIM RCV000012711 SCV000032946 pathogenic Hyperimmunoglobulin D with periodic fever 1999-06-01 no assertion criteria provided literature only

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