Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002513892 | SCV003524171 | likely pathogenic | Cryopyrin associated periodic syndrome | 2022-08-19 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Gly757 amino acid residue in NLRP3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18063752, 18080732, 21702021, 23015306, 29152264). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 97959). This variant is also known as 2264G>C (G755A). This missense change has been observed in individuals with clinical features of cryopyrin-associated periodic syndrome (PMID: 16871551, 24773462; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 757 of the NLRP3 protein (p.Gly757Ala). |
| Unité médicale des maladies autoinflammatoires, |
RCV000084220 | SCV000116354 | not provided | Familial cold autoinflammatory syndrome 1 | no assertion provided | not provided |