ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.697A>T (p.Lys233Ter)

gnomAD frequency: 0.00004  dbSNP: rs121918197
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000367935 SCV000397838 uncertain significance RPGRIP1L-related disorder 2017-04-28 criteria provided, single submitter clinical testing The RPGRIP1L c.697A>T (p.Lys233Ter) variant is a stop-gained variant that is predicted to result in premature termination of the protein. The p.Lys233Ter variant has been reported in one study in which it is found in one individual with cerebello-oculo-renal syndrome (also known as Joubert syndrome type B) in a compound heterozygous state with a missense variant (Delous et al. 2007). The p.Lys233Ter variant was absent from 260 control chromosomes but is reported at a frequency of 0.00002478 in the total population from the Exome Aggregation Consortium. Due to the potential impact of stop-gained variants and supporting evidence, the p.Lys233Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for RPGRIP1L-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp RCV001385849 SCV001585843 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome 2023-12-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys233*) 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 (rs121918197, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with Joubert syndrome (PMID: 17558409). ClinVar contains an entry for this variant (Variation ID: 1068). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV001781156 SCV002019893 pathogenic not provided 2019-09-13 criteria provided, single submitter clinical testing
OMIM RCV000001123 SCV000021273 pathogenic Joubert syndrome 7 2007-07-01 no assertion criteria provided literature only
Natera, Inc. RCV001831499 SCV002085757 pathogenic Familial aplasia of the vermis 2020-02-20 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV000367935 SCV005356274 pathogenic RPGRIP1L-related disorder 2024-05-07 no assertion criteria provided clinical testing The RPGRIP1L c.697A>T variant is predicted to result in premature protein termination (p.Lys233*). This variant has been reported in the compound heterozygous state in individuals with a variety of phenotypes, including Joubert syndrome (Delous et al. 2007. PubMed ID: 17558409), neurodegeneration with brain iron accumulation (NBIA; Martínez-Rubio et al. 2022. PubMed ID: 36233161) and inherited retinal disease (Table S3, Hanany et al. 2020. PubMed ID: 31964843). This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD. Nonsense variants in RPGRIP1L are expected to be pathogenic. This variant is interpreted as pathogenic.

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