Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratorio de Genetica e Diagnostico Molecular, |
RCV002252565 | SCV002523866 | uncertain significance | See cases | 2020-11-25 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2 |
Labcorp Genetics |
RCV003094155 | SCV002930310 | uncertain significance | Familial cold autoinflammatory syndrome 2 | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 612 of the NLRP12 protein (p.Glu612Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. ClinVar contains an entry for this variant (Variation ID: 1690973). 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. |
Prevention |
RCV003408185 | SCV004114074 | uncertain significance | NLRP12-related disorder | 2022-11-07 | criteria provided, single submitter | clinical testing | The NLRP12 c.1834G>A variant is predicted to result in the amino acid substitution p.Glu612Lys. 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. |