Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000685494 | SCV000812977 | uncertain significance | Familial cold autoinflammatory syndrome 2 | 2022-08-09 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. ClinVar contains an entry for this variant (Variation ID: 565835). This missense change has been observed in individual(s) with familial cold autoinflammatory syndrome (PMID: 29500522). This variant is present in population databases (rs374108426, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 211 of the NLRP12 protein (p.Arg211His). |
Genome Diagnostics Laboratory, |
RCV002263929 | SCV002542560 | uncertain significance | Autoinflammatory syndrome | 2021-11-26 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003892528 | SCV004716193 | uncertain significance | NLRP12-related disorder | 2023-10-18 | criteria provided, single submitter | clinical testing | The NLRP12 c.632G>A variant is predicted to result in the amino acid substitution p.Arg211His. This variant, in addition to other variants in NLRP3 and NOD2, was reported in an individual with NLRP12-related autoinflammatory disease (P3, Kostik et al. 2018. PubMed ID: 29500522). This variant is reported in 0.0065% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-54314281-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |