Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000204506 | SCV000260433 | uncertain significance | Bardet-Biedl syndrome | 2022-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 496 of the BBS9 protein (p.Thr496Ile). This variant is present in population databases (rs139303948, gnomAD 0.03%). 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: 220123). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
Fulgent Genetics, |
RCV002494525 | SCV002777752 | uncertain significance | Bardet-Biedl syndrome 9 | 2022-02-19 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002515522 | SCV003580366 | uncertain significance | Inborn genetic diseases | 2022-05-31 | criteria provided, single submitter | clinical testing | The c.1487C>T (p.T496I) alteration is located in exon 14 (coding exon 13) of the BBS9 gene. This alteration results from a C to T substitution at nucleotide position 1487, causing the threonine (T) at amino acid position 496 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Preventiongenetics, |
RCV003417743 | SCV004108557 | uncertain significance | BBS9-related condition | 2023-08-01 | criteria provided, single submitter | clinical testing | The BBS9 c.1487C>T variant is predicted to result in the amino acid substitution p.Thr496Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.028% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-33390885-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |