ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.830G>A (p.Arg277His) (rs104895352)

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Total submissions: 2
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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 2018-12-04 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 277 of the MVK protein (p.Arg277His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs104895352, ExAC 0.001%). This variant has been reported to segregate with hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) in a family (PMID: 16255052). ClinVar contains an entry for this variant (Variation ID: 97631). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
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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