Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001055437 | SCV001219830 | uncertain significance | Bardet-Biedl syndrome | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 23 of the BBS12 protein (p.Ala23Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs371153231, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with BBS12-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The threonine 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. |
Prevention |
RCV003906160 | SCV004725965 | uncertain significance | BBS12-related condition | 2023-12-05 | criteria provided, single submitter | clinical testing | The BBS12 c.67G>A variant is predicted to result in the amino acid substitution p.Ala23Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.036% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Natera, |
RCV001275673 | SCV001460976 | uncertain significance | Bardet-Biedl syndrome 12 | 2020-09-16 | no assertion criteria provided | clinical testing |