Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001227276 | SCV001399628 | pathogenic | Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever | 2023-08-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly376 amino acid residue in MVK. Other variant(s) that disrupt this residue have been observed in individuals with MVK-related conditions (PMID: 15536479), which suggests that this may be a clinically significant amino acid residue. 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 expected to disrupt MVK protein function. ClinVar contains an entry for this variant (Variation ID: 954760). This missense change has been observed in individual(s) with mevalonate kinase deficiency and/or disseminated superficial actinic porokeratosis (PMID: 21708801, 22983302, 30148429). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 376 of the MVK protein (p.Gly376Ser). |