Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000012930 | SCV000807218 | likely pathogenic | Bardet-Biedl syndrome 1 | criteria provided, single submitter | clinical testing | ||
| Invitae | RCV001055313 | SCV001219700 | pathogenic | Bardet-Biedl syndrome | 2023-11-04 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 518 of the BBS1 protein (p.Leu518Pro). This variant is present in population databases (rs121917778, gnomAD 0.003%). This missense change has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 12524598, 12920096). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 12147). 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 not expected to disrupt BBS1 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Blueprint Genetics | RCV001075155 | SCV001240767 | pathogenic | Retinal dystrophy | 2018-10-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001753415 | SCV001986115 | uncertain significance | not provided | 2019-12-31 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed multiple times with a pathogenic variant (M390R) in unrelated patients with BBS in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Mykytyn et al., 2003; Fauser et al., 2003); This variant is associated with the following publications: (PMID: 25326635, 12524598, 12920096, 21463199, 17065520) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001055313 | SCV002572146 | likely pathogenic | Bardet-Biedl syndrome | 2022-08-18 | criteria provided, single submitter | clinical testing | Variant summary: BBS1 c.1553T>C (p.Leu518Pro) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251494 control chromosomes (gnomAD). c.1553T>C has been reported in the literature in multiple bi-allelic individuals (with p.M390R) affected with Bardet-Biedl Syndrome (examples: Mykytyn_2003, Fauser_2003, Azari_2006, and Haer-Wigman_2017). These data indicate that the variant is very likely to be associated with disease. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=3) and pathogenic (n=2). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| OMIM | RCV000012930 | SCV000033171 | pathogenic | Bardet-Biedl syndrome 1 | 2003-02-01 | no assertion criteria provided | literature only | |
| Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000012930 | SCV000804597 | uncertain significance | Bardet-Biedl syndrome 1 | 2016-09-01 | no assertion criteria provided | clinical testing |