ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.830G>A (p.Arg277His)

gnomAD frequency: 0.00002  dbSNP: rs104895352
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Total submissions: 4
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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, The Hospital for Sick Children RCV002262665 SCV002542347 likely pathogenic Autoinflammatory syndrome 2019-11-01 criteria provided, single submitter clinical testing
Fulgent Genetics, 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, CHRU Montpellier RCV000083883 SCV000115989 not provided Hyperimmunoglobulin D with periodic fever no assertion provided not provided

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