Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001232168 | SCV001404714 | uncertain significance | Cryopyrin associated periodic syndrome | 2019-09-18 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with valine at codon 54 of the NLRP3 protein (p.Leu54Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NLRP3-related conditions. This variant is not present in population databases (ExAC no frequency). |
Prevention |
RCV003426006 | SCV004108921 | uncertain significance | NLRP3-related condition | 2022-09-28 | criteria provided, single submitter | clinical testing | The NLRP3 c.160C>G variant is predicted to result in the amino acid substitution p.Leu54Val. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |