Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000462368 | SCV000553796 | likely pathogenic | Bardet-Biedl syndrome | 2018-06-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with valine at codon 277 of the BBS4 protein (p.Gly277Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs749017489, ExAC 0.009%). This variant has been observed in individuals with clinical features consistent with Bardet-Biedl syndrome (Invitae). It has also been observed to segregate with Bardet-Biedl syndrome in a family (Invitae). ClinVar contains an entry for this variant (Variation ID: 412297). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). The observation of one or more missense substitutions at this codon (p.Gly277Arg) in affected individuals suggests that this may be a clinically significant residue (PMID: 24849935). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |