Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000793644 | SCV000933008 | uncertain significance | Bardet-Biedl syndrome | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 46 of the BBS9 protein (p.Met46Ile). This variant is present in population databases (rs145241295, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with BBS9-related conditions. ClinVar contains an entry for this variant (Variation ID: 640590). 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 BBS9 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 |
RCV003955508 | SCV004772215 | uncertain significance | BBS9-related condition | 2024-01-17 | criteria provided, single submitter | clinical testing | The BBS9 c.3G>A variant is predicted to disrupt the translation initiation site (Start loss). To our knowledge, this variant has not been reported in the literature, but has been reported in ClinVar as a variant of uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/640590/). This variant is reported in 0.040% 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. |