ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.3529C>T (p.Arg1177Ter)

gnomAD frequency: 0.00002  dbSNP: rs778533826
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UW Hindbrain Malformation Research Program, University of Washington RCV000201661 SCV000256467 pathogenic Joubert syndrome 7 2015-02-23 criteria provided, single submitter research
Invitae RCV001853237 SCV002229404 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome 2023-10-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1177*) 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 (rs778533826, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with clinical features of Joubert syndrome (PMID: 26092869). ClinVar contains an entry for this variant (Variation ID: 217694). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002492927 SCV002800733 pathogenic Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 2022-04-24 criteria provided, single submitter clinical testing
GeneDx RCV002509297 SCV002818854 pathogenic not provided 2022-07-08 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 significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26092869)
Ambry Genetics RCV002517313 SCV003722023 pathogenic Inborn genetic diseases 2022-07-21 criteria provided, single submitter clinical testing The c.3529C>T (p.R1177*) alteration, located in exon 24 (coding exon 23) of the RPGRIP1L gene, consists of a C to T substitution at nucleotide position 3529. This changes the amino acid from a arginine (R) to a stop codon at amino acid position 1177. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of <0.01% (4/251476) total alleles studied. The highest observed frequency was <0.01% (1/30616) of South Asian alleles. This variant was identified in one individual with Joubert syndrome in conjunction with a second RPGRIP1L variant (Bachmann-Gagescu, 2015). Based on the available evidence, this alteration is classified as pathogenic.

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