Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001123248 | SCV001282068 | benign | Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. |
Invitae | RCV001123248 | SCV001386959 | uncertain significance | Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 378 of the IL12RB1 protein (p.Gly378Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs401502, ExAC 0.006%). This missense change has been observed in individual(s) with mycobacterial disease (PMID: 11313259, 11992283, 16088278). 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 arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect IL12RB1 function (PMID: 21057261). 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. |