Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000305416 | SCV000373273 | uncertain significance | Bardet-Biedl syndrome 1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV001212347 | SCV001383930 | uncertain significance | Bardet-Biedl syndrome | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 380 of the BBS1 protein (p.Arg380Trp). This variant is present in population databases (rs752299442, gnomAD 0.003%). 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: 305467). 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 BBS1 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. |
| Natera, |
RCV000305416 | SCV002094757 | uncertain significance | Bardet-Biedl syndrome 1 | 2020-12-10 | no assertion criteria provided | clinical testing | |
| Prevention |
RCV003957580 | SCV004769741 | uncertain significance | BBS1-related disorder | 2024-07-07 | no assertion criteria provided | clinical testing | The BBS1 c.1138C>T variant is predicted to result in the amino acid substitution p.Arg380Trp. To our knowledge, this variant has not been reported in the literature. An alternate substitution impacting the same amino acid (p.Arg380Gln) was reported in the homozygous state in two related individuals with Joubert syndrome; however, both individuals were also homozygous for a variant in the TMEM138 gene (Suzuki et al. 2016. PubMed ID: 27434533). The c.1138C>T (p.Arg380Trp) variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |