Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001246356 | SCV001419703 | uncertain significance | Bardet-Biedl syndrome | 2022-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 245 of the BBS1 protein (p.Pro245Leu). This variant is present in population databases (rs151203205, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with BBS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 970728). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Fulgent Genetics, |
RCV001835263 | SCV002781959 | uncertain significance | Bardet-Biedl syndrome 1 | 2022-05-31 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003938576 | SCV004756142 | uncertain significance | BBS1-related condition | 2023-11-27 | criteria provided, single submitter | clinical testing | The BBS1 c.734C>T variant is predicted to result in the amino acid substitution p.Pro245Leu. This variant was previously reported in the heterozygous state in one individual with Bardet-Biedl syndrome; a second causative variant was not detected in the same gene (Janssen et al. 2011. PubMed ID: 21052717). In a second study, this variant was found along with a second variant in MKS1 in a patient presenting with non-obese juvenile-onset diabetes, learning difficulties, speech delay, short stature, and brachydactyly (Dallali et al. 2021. PubMed ID: 34691137). Dallali et al. suggest a possible oligogenic inheritance pattern for Bardet-Biedl syndrome. This variant is reported in 0.10% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-66288751-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Natera, |
RCV001835263 | SCV002094739 | uncertain significance | Bardet-Biedl syndrome 1 | 2020-03-21 | no assertion criteria provided | clinical testing |