Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Fulgent Genetics, |
RCV002486475 | SCV002781707 | uncertain significance | Bardet-Biedl syndrome 9 | 2022-05-17 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002547594 | SCV003298088 | uncertain significance | Bardet-Biedl syndrome | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 451 of the BBS9 protein (p.Ile451Thr). This variant is present in population databases (rs773192233, gnomAD 0.003%). 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: 1049097). 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 with a negative predictive value of 80%. 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. |
| Ambry Genetics | RCV003246928 | SCV003938590 | uncertain significance | Inborn genetic diseases | 2023-05-16 | criteria provided, single submitter | clinical testing | The c.1352T>C (p.I451T) alteration is located in exon 13 (coding exon 12) of the BBS9 gene. This alteration results from a T to C substitution at nucleotide position 1352, causing the isoleucine (I) at amino acid position 451 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Department of Pathology and Laboratory Medicine, |
RCV001354753 | SCV001549445 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The BBS9 p.Ile360Thr variant was not identified in the literature nor was it identified in ClinVar, Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs773192233) and in control databases in 3 of 251260 chromosomes at a frequency of 0.000012 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following population: European (non-Finnish) in 3 of 113612 chromosomes (freq: 0.000026); it was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other or South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Ile360 residue is not conserved in mammals and computational analyses (SIFT, AlignGVGD, BLOSUM, PolyPhen-2, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |