Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000541640 | SCV000646326 | uncertain significance | Familial cold autoinflammatory syndrome 2 | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 52 of the NLRP12 protein (p.Gly52Ser). This variant is present in population databases (rs369053968, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of familial cold autoinflammatory syndrome (FCAS) (PMID: 29500522). ClinVar contains an entry for this variant (Variation ID: 469089). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NLRP12 protein function with a negative predictive value of 80%. 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. |
Gene |
RCV001755852 | SCV001994935 | uncertain significance | not provided | 2020-01-31 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29500522, 30783801) |
Genome Diagnostics Laboratory, |
RCV002263784 | SCV002542455 | uncertain significance | Autoinflammatory syndrome | 2018-05-01 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV001755852 | SCV004225439 | uncertain significance | not provided | 2022-02-17 | criteria provided, single submitter | clinical testing | BP4 |