Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000645637 | SCV000767387 | uncertain significance | Familial cold autoinflammatory syndrome 2 | 2023-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 444 of the NLRP12 protein (p.Gln444Glu). This variant is present in population databases (rs371528857, gnomAD 0.002%). 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: 536925). 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. 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. |
Baylor Genetics | RCV000645637 | SCV001522054 | uncertain significance | Familial cold autoinflammatory syndrome 2 | 2019-03-14 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Ambry Genetics | RCV002530019 | SCV003697622 | uncertain significance | Inborn genetic diseases | 2022-05-13 | criteria provided, single submitter | clinical testing | The c.1330C>G (p.Q444E) alteration is located in exon 3 (coding exon 3) of the NLRP12 gene. This alteration results from a C to G substitution at nucleotide position 1330, causing the glutamine (Q) at amino acid position 444 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |