ClinVar Miner

Submissions for variant NM_004895.4(NLRP3):c.230C>T (p.Ala77Val) (rs200288250)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000213778 SCV000278932 uncertain significance not specified 2017-08-28 criteria provided, single submitter clinical testing The A77V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is observed in 8/65994 (0.011%) alleles from individuals of European background in the ExAC dataset (Lek et al., 2016). A77V is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000690646 SCV000818343 uncertain significance Cryopyrin associated periodic syndrome 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 77 of the NLRP3 protein (p.Ala77Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs200288250, ExAC 0.01%). This variant has not been reported in the literature in individuals with NLRP3-related disease. ClinVar contains an entry for this variant (Variation ID: 234286). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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