Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001052996 | SCV001217236 | pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser768*) in the RPGRIP1L gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RPGRIP1L are known to be pathogenic (PMID: 17558409). 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 RPGRIP1L-related conditions. ClinVar contains an entry for this variant (Variation ID: 849109). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323789 | SCV004029135 | pathogenic | Joubert syndrome and related disorders | 2023-07-12 | criteria provided, single submitter | clinical testing | Variant summary: RPGRIP1L c.2303C>A (p.Ser768X) 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. The variant allele was found at a frequency of 8e-06 in 251378 control chromosomes. To our knowledge, no occurrence of c.2303C>A in individuals affected with Joubert Syndrome And Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Fulgent Genetics, |
RCV005021379 | SCV005642063 | likely pathogenic | Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 | 2024-04-15 | criteria provided, single submitter | clinical testing |