Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000803838 | SCV000943725 | likely pathogenic | Cryopyrin associated periodic syndrome | 2021-03-08 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 527 of the NLRP3 protein (p.Glu527Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant has been observed in several individuals affected with NLRP3-related disease (PMID: 16081838; 20472245; 29378952; 26245507). This variant is also known as p.Glu525Lys in the literature. ClinVar contains an entry for this variant (Variation ID: 97939). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. |
Unité médicale des maladies autoinflammatoires, |
RCV000084198 | SCV000116331 | not provided | Familial cold autoinflammatory syndrome 1 | no assertion provided | not provided |