ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.790C>T (p.Leu264Phe)

gnomAD frequency: 0.00003  dbSNP: rs104895315
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001381670 SCV001580162 pathogenic Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 264 of the MVK protein (p.Leu264Phe). This variant is present in population databases (rs104895315, gnomAD 0.06%). This missense change has been observed in individual(s) with clinical features of mevalonate kinase deficiency and mevalonate kinase deficiency (PMID: 10417275, 11313768, 19786432, 22038276, 22566169, 29047407). ClinVar contains an entry for this variant (Variation ID: 97625). 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 with a negative predictive value of 80%. Experimental studies have shown that this missense change affects MVK function (PMID: 10417275). For these reasons, this variant has been classified as Pathogenic.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000083877 SCV000115982 not provided Hyperimmunoglobulin D with periodic fever no assertion provided not provided

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