Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001381670 | SCV001580162 | pathogenic | Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 264 of the MVK protein (p.Leu264Phe). This variant is present in population databases (rs104895315, gnomAD 0.06%). This missense change has been observed in individual(s) with clinical features of mevalonate kinase deficiency and mevalonate kinase deficiency (PMID: 10417275, 11313768, 19786432, 22038276, 22566169, 29047407). ClinVar contains an entry for this variant (Variation ID: 97625). 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 not expected to disrupt MVK protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects MVK function (PMID: 10417275). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004700401 | SCV005202931 | pathogenic | Mevalonic aciduria | 2024-07-23 | criteria provided, single submitter | clinical testing | Variant summary: MVK c.790C>T (p.Leu264Phe) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251458 control chromosomes (gnomAD). c.790C>T has been reported in the literature in multiple individuals affected with Mevalonic aciduria (e.g. Hinson_1999, Houten_2001). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, finding that the variant results in a severe loss of protein expression and enzymatic activity (Hinson_1999). The following publications have been ascertained in the context of this evaluation (PMID: 10417275, 11313768). ClinVar contains an entry for this variant (Variation ID: 97625). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Unité médicale des maladies autoinflammatoires, |
RCV000083877 | SCV000115982 | not provided | Hyperimmunoglobulin D with periodic fever | no assertion provided | not provided |