ClinVar Miner

Submissions for variant NM_001243133.2(NLRP3):c.1021G>A (p.Glu341Lys)

gnomAD frequency: 0.00005  dbSNP: rs369910640
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493260 SCV000581816 uncertain significance not provided 2017-05-04 criteria provided, single submitter clinical testing The E343K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). E343K 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 not conserved; however, this domain is a major locus for CAPS-associated pathogenic variants (Masters et al., 2009). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to 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 RCV001865536 SCV002281431 uncertain significance Cryopyrin associated periodic syndrome 2023-07-07 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 429286). This variant has not been reported in the literature in individuals affected with NLRP3-related conditions. This variant is present in population databases (rs369910640, gnomAD 0.01%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 343 of the NLRP3 protein (p.Glu343Lys).
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002263701 SCV002542582 uncertain significance Autoinflammatory syndrome 2019-12-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002496892 SCV002814002 uncertain significance Chronic infantile neurological, cutaneous and articular syndrome; Keratitis fugax hereditaria; Familial amyloid nephropathy with urticaria AND deafness; Familial cold autoinflammatory syndrome 1; Hearing loss, autosomal dominant 34, with or without inflammation 2022-04-26 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000493260 SCV003815957 uncertain significance not provided 2022-05-30 criteria provided, single submitter clinical testing

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