Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001067857 | SCV001232938 | pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2023-04-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1070). This premature translational stop signal has been observed in individual(s) with Joubert syndrome type B (PMID: 17558409). This variant is present in population databases (rs121918199, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gln253*) 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). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003398409 | SCV004122144 | pathogenic | Joubert syndrome and related disorders | 2023-10-25 | criteria provided, single submitter | clinical testing | Variant summary: RPGRIP1L c.757C>T (p.Gln253X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 4e-06 in 250894 control chromosomes (gnomAD). c.757C>T has been reported in the literature in individuals affected with Joubert Syndrome (e.g. Ying_2022). The following publication has been ascertained in the context of this evaluation (PMID: 35858853). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Fulgent Genetics, |
RCV005016221 | SCV005643935 | pathogenic | Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 | 2024-03-08 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000001125 | SCV000021275 | pathogenic | Joubert syndrome 7 | 2007-07-01 | no assertion criteria provided | literature only | |
| Natera, |
RCV001831500 | SCV002085754 | pathogenic | Familial aplasia of the vermis | 2021-08-18 | no assertion criteria provided | clinical testing |