Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
RCV001199008 | SCV001370003 | likely pathogenic | Joubert syndrome 7 | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2. |
Labcorp Genetics |
RCV001241219 | SCV001414224 | pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg602*) 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). This variant is present in population databases (rs745413543, gnomAD 0.006%). 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: 931963). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002509625 | SCV002819317 | likely pathogenic | Joubert syndrome and related disorders | 2022-12-01 | criteria provided, single submitter | clinical testing | Variant summary: RPGRIP1L c.1804C>T (p.Arg602X) 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 2e-05 in 250176 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1804C>T in individuals affected with Joubert Syndrome And Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported in the literature. Two submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as either pathogenic (n=1) or likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic. |