Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000778712 | SCV001394703 | pathogenic | Joubert syndrome 8 | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn277Lysfs*9) in the ARL13B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARL13B are known to be pathogenic (PMID: 18674751). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ARL13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 631931). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001805846 | SCV002050783 | likely pathogenic | Joubert syndrome and related disorders | 2021-12-01 | criteria provided, single submitter | clinical testing | Variant summary: ARL13B c.830dupA (p.Asn277LysfsX9) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic in ClinVar database. The variant allele was found at a frequency of 0.00012 in 241834 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in ARL13B causing Joubert Syndrome And Related Disorders (0.00012 vs 0.0004), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.830dupA in individuals affected with Joubert Syndrome And Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance and pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV000778712 | SCV002061409 | likely pathogenic | Joubert syndrome 8 | 2021-07-06 | criteria provided, single submitter | clinical testing | PVS1, PM2 |