ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.1603C>T (p.Arg535Cys)

gnomAD frequency: 0.00009  dbSNP: rs149781516
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001246611 SCV001419981 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-09-07 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 535 of the RPGRIP1L protein (p.Arg535Cys). This variant is present in population databases (rs149781516, gnomAD 0.03%). 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: 970944). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Fulgent Genetics, Fulgent Genetics RCV002484380 SCV002791600 uncertain significance Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 2024-04-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV002570345 SCV003607045 uncertain significance Inborn genetic diseases 2022-03-29 criteria provided, single submitter clinical testing The c.1603C>T (p.R535C) alteration is located in exon 14 (coding exon 13) of the RPGRIP1L gene. This alteration results from a C to T substitution at nucleotide position 1603, causing the arginine (R) at amino acid position 535 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV004762020 SCV005371284 uncertain significance not provided 2023-06-13 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001835274 SCV002085727 uncertain significance Familial aplasia of the vermis 2020-05-08 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004538519 SCV004113965 uncertain significance RPGRIP1L-related disorder 2023-12-21 no assertion criteria provided clinical testing The RPGRIP1L c.1603C>T variant is predicted to result in the amino acid substitution p.Arg535Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.036% of alleles in individuals of African 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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