Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
RCV002263701 | SCV002542582 | uncertain significance | Autoinflammatory syndrome | 2019-12-01 | criteria provided, single submitter | clinical testing | |
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, |
RCV000493260 | SCV003815957 | uncertain significance | not provided | 2022-05-30 | criteria provided, single submitter | clinical testing |