ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser329 amino acid residue in MVK. Other variant(s) that disrupt this residue have been observed in individuals with MVK-related conditions (PMID: 16707534), 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: 848443). This missense change has been observed in individual(s) with clinical features of mevalonate kinase deficiency (PMID: 13130485, 27213830; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 329 of the MVK protein (p.Ser329Arg).