Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001042718 | SCV001206418 | likely pathogenic | Bardet-Biedl syndrome | 2023-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 289 of the BBS12 protein (p.Ala289Pro). This variant is present in population databases (rs121918328, gnomAD 0.003%). This missense change has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 17160889). ClinVar contains an entry for this variant (Variation ID: 1150). 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 expected to disrupt BBS12 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects BBS12 function (PMID: 20080638, 20498079). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Blueprint Genetics | RCV001073577 | SCV001239128 | uncertain significance | Retinal dystrophy | 2019-06-29 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000001209 | SCV000021359 | pathogenic | Bardet-Biedl syndrome 12 | 2007-01-01 | no assertion criteria provided | literature only | |
Natera, |
RCV000001209 | SCV002082494 | likely pathogenic | Bardet-Biedl syndrome 12 | 2020-07-08 | no assertion criteria provided | clinical testing |