ClinVar Miner

Submissions for variant NM_004895.4(NLRP3):c.1313C>T (p.Thr438Ile) (rs180177433)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001056510 SCV001220954 pathogenic Cryopyrin associated periodic syndrome 2019-03-13 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 438 of the NLRP3 protein (p.Thr438Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with cryopyrin-associated periodic syndromes (CAPS) (PMID: 28501347, 29988644, 26931528, 29047407, 18080732). ClinVar contains an entry for this variant (Variation ID: 97924). In the literature, this variant is also referred to as 1307C>T and T436I. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Thr438 amino acid residue in NLRP3. Other variant(s) that disrupt this residue have been observed in individuals with NLRP3-related conditions (PMID: 12032915, 26245507, 25979514, 17513575, 27191192), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000084183 SCV000116315 not provided Familial cold urticaria no assertion provided not provided

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