Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000693669 | SCV000821547 | pathogenic | Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 277 of the MVK protein (p.Arg277His). This variant is present in population databases (rs104895352, gnomAD 0.008%). This missense change has been observed in individual(s) with hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) (PMID: 16255052). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 97631). 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. This variant disrupts the p.Arg277 amino acid residue in MVK. Other variant(s) that disrupt this residue have been observed in individuals with MVK-related conditions (PMID: 11111075, 16835861, 24656624), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Genome Diagnostics Laboratory, |
RCV002262665 | SCV002542347 | likely pathogenic | Autoinflammatory syndrome | 2019-11-01 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000693669 | SCV002790646 | likely pathogenic | Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever | 2021-11-30 | criteria provided, single submitter | clinical testing | |
Unité médicale des maladies autoinflammatoires, |
RCV000083883 | SCV000115989 | not provided | Hyperimmunoglobulin D with periodic fever | no assertion provided | not provided |