Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001364998 | SCV001561214 | uncertain significance | Familial cold autoinflammatory syndrome 2 | 2023-09-23 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1056209). This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. This variant is present in population databases (rs151187420, gnomAD 0.007%). This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 989 of the NLRP12 protein (p.Asn989Thr). |
Genome Diagnostics Laboratory, |
RCV002264282 | SCV002542532 | uncertain significance | Autoinflammatory syndrome | 2021-01-13 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV001364998 | SCV004565208 | uncertain significance | Familial cold autoinflammatory syndrome 2 | 2023-06-28 | criteria provided, single submitter | clinical testing | The NLRP12 c.2966A>C; p.Asn989Thr variant (rs151187420), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1056209). This variant is only observed on three alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. Computational analyses predict that this variant is neutral (REVEL: 0.043). However, given the lack of clinical and functional data, the significance of this variant is uncertain at this time. |