Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001205616 | SCV001376883 | pathogenic | Bardet-Biedl syndrome 3; Retinitis pigmentosa 55 | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 167 of the ARL6 protein (p.Gly167Arg). This variant is present in population databases (rs764523283, gnomAD 0.003%). This missense change has been observed in individual(s) with ARL6-related conditions (PMID: 32483926; Invitae). ClinVar contains an entry for this variant (Variation ID: 936753). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV003938562 | SCV004764423 | uncertain significance | ARL6-related condition | 2024-01-24 | criteria provided, single submitter | clinical testing | The ARL6 c.499G>A variant is predicted to result in the amino acid substitution p.Gly167Arg. To our knowledge, this variant has not been reported in individuals with Bardet-Biedl syndrome. However, this variant has been reported in the compound heterozygous state in a patient with retinitis pigmentosa type 55 (Diñeiro et al. 2020. PubMed ID: 32483926). This 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. |