Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Clinical Services Laboratory, |
RCV000778712 | SCV000915066 | uncertain significance | Joubert syndrome 8 | 2017-10-24 | criteria provided, single submitter | clinical testing | The ARL13B c.830dupA (p.Asn277LysfsTer9) variant results in a frameshift and is predicted to result in premature termination of the protein. It was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene and cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for Joubert syndrome. |
| Invitae | RCV000778712 | SCV001394703 | pathogenic | Joubert syndrome 8 | 2019-10-23 | 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. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with ARL13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 631931). Loss-of-function variants in ARL13B are known to be pathogenic (PMID: 18674751). For these reasons, this variant has been classified as Pathogenic. |