ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.1489G>T (p.Glu497Ter)

gnomAD frequency: 0.00001  dbSNP: rs756821449
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000365145 SCV000329500 pathogenic not provided 2023-02-09 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); Has not been previously published as a germline pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 17558409, 25032700)
Labcorp Genetics (formerly Invitae), Labcorp RCV000797386 SCV000936940 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome 2024-11-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu497*) 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 (rs756821449, gnomAD 0.003%). 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: 279885). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005008228 SCV005642108 likely pathogenic Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 2024-05-10 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004535245 SCV004717386 likely pathogenic RPGRIP1L-related disorder 2024-01-04 no assertion criteria provided clinical testing The RPGRIP1L c.1489G>T variant is predicted to result in premature protein termination (p.Glu497*). This variant was reported in an individual from an obesity cohort; however, detailed clinical information was not available (Table S2, Al-Humadi et al. 2023. PubMed ID: 37835041). This variant is reported in 0.0044% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Nonsense variants in RPGRIP1L are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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