Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000804120 | SCV000944015 | pathogenic | Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever | 2023-11-05 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 20 of the MVK protein (p.His20Asn). This variant is present in population databases (rs11544299, gnomAD 0.1%). This missense change has been observed in individual(s) with MVK-related conditions (PMID: 11313769, 27213830, 28501347). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 649235). 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 with a positive predictive value of 80%. This variant disrupts the p.His20 amino acid residue in MVK. Other variant(s) that disrupt this residue have been observed in individuals with MVK-related conditions (PMID: 10369261, 15536479, 16835861, 27213830, 29047407), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |