Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
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 | For these reasons, this allele has been classified as Likely Pathogenic. 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. 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). This variant is not present in population databases (ExAC no frequency). 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. |
OMIM | RCV000012711 | SCV000032946 | pathogenic | Hyperimmunoglobulin D with periodic fever | 1999-06-01 | no assertion criteria provided | literature only |