ClinVar Miner

Submissions for variant NM_004895.4(NLRP3):c.916G>A (p.Glu306Lys) (rs180177484)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000217940 SCV000278939 pathogenic not provided 2017-04-27 criteria provided, single submitter clinical testing The E306K variant has been published previously in association with NLRP3-related disorders (Caroli et al., 2007; Mehr et al., 2016). The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). E306K is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position within the NACHT domain that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, functional studies have shown E306K impairs the negative regulation activity of the NLRP3 protein (Mortimer et al., 2016). Missense variants in nearby residues (M301V, G303D/A, F304L, D305H/N/G, L307P, Q308K, G309S, F311S) have been reported in the Human Gene Mutation Database in association with NLRP3-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. In summary, we consider this variant to be pathogenic.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000084243 SCV000116379 not provided Familial cold urticaria no assertion provided not provided

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