Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV000513470 | SCV000608920 | uncertain significance | not provided | 2017-05-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000807944 | SCV000948024 | uncertain significance | Familial cold autoinflammatory syndrome 2 | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 728 of the NLRP12 protein (p.Arg728Gln). This variant is present in population databases (rs373285006, gnomAD 0.006%). 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: 444482). 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. |
| Illumina Laboratory Services, |
RCV000807944 | SCV001293776 | benign | Familial cold autoinflammatory syndrome 2 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
| ARUP Laboratories, |
RCV000807944 | SCV001470945 | uncertain significance | Familial cold autoinflammatory syndrome 2 | 2021-04-17 | criteria provided, single submitter | clinical testing | The NLRP12 c.2183G>A; p.Arg728Gln variant (rs373285006), to our knowledge, is not reported in the medical literature. The variant is reported in the ClinVar database (Variation ID: 444482) and in the general population with an overall allele frequency of 0.004% (11/282,644 alleles) in the Genome Aggregation Database. The arginine at codon 728 is moderately conserved but computational analyses predict that this variant is neutral (REVEL: 0.133). Due to limited information, the clinical significance of the p.Arg728Gln variant is uncertain at this time. |
| MGZ Medical Genetics Center | RCV000807944 | SCV002579059 | uncertain significance | Familial cold autoinflammatory syndrome 2 | 2022-04-11 | criteria provided, single submitter | clinical testing |