ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.205C>T (p.Arg69Cys)

gnomAD frequency: 0.00001  dbSNP: rs775007896
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001570276 SCV001794545 uncertain significance not provided 2019-07-18 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as a germline pathogenic or benign variant to our knowledge; This variant is associated with the following publications: (PMID: 22810696)
Fulgent Genetics, Fulgent Genetics RCV002480923 SCV002776142 uncertain significance Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 2021-12-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002537891 SCV003295191 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-06-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 69 of the RPGRIP1L protein (p.Arg69Cys). This variant is present in population databases (rs775007896, gnomAD 0.008%). 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: 992047). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc. RCV001280363 SCV001467539 uncertain significance Familial aplasia of the vermis 2020-08-24 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004538560 SCV004113077 uncertain significance RPGRIP1L-related disorder 2024-03-26 no assertion criteria provided clinical testing The RPGRIP1L c.205C>T variant is predicted to result in the amino acid substitution p.Arg69Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0077% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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