Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001210878 | SCV001382387 | uncertain significance | Bardet-Biedl syndrome | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 191 of the BBS4 protein (p.Tyr191Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs756915341, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with BBS4-related conditions. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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, |
RCV002484146 | SCV002775389 | uncertain significance | Bardet-Biedl syndrome 4 | 2021-07-28 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002561745 | SCV003555654 | uncertain significance | Inborn genetic diseases | 2021-01-08 | criteria provided, single submitter | clinical testing | The c.572A>G (p.Y191C) alteration is located in exon 8 (coding exon 8) of the BBS4 gene. This alteration results from a A to G substitution at nucleotide position 572, causing the tyrosine (Y) at amino acid position 191 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003414003 | SCV004107906 | uncertain significance | BBS4-related condition | 2023-01-31 | criteria provided, single submitter | clinical testing | The BBS4 c.572A>G variant is predicted to result in the amino acid substitution p.Tyr191Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-73016981-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |