ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.3545C>T (p.Pro1182Leu)

gnomAD frequency: 0.00001  dbSNP: rs1446510817
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001314393 SCV001504926 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1182 of the RPGRIP1L protein (p.Pro1182Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with RPGRIP1L-related conditions. 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.
Ambry Genetics RCV004034311 SCV005015374 uncertain significance Inborn genetic diseases 2023-10-16 criteria provided, single submitter clinical testing The c.3545C>T (p.P1182L) alteration is located in exon 24 (coding exon 23) of the RPGRIP1L gene. This alteration results from a C to T substitution at nucleotide position 3545, causing the proline (P) at amino acid position 1182 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001836291 SCV002087504 uncertain significance Familial aplasia of the vermis 2020-02-04 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004733247 SCV005365975 uncertain significance RPGRIP1L-related disorder 2024-04-17 no assertion criteria provided clinical testing The RPGRIP1L c.3545C>T variant is predicted to result in the amino acid substitution p.Pro1182Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0033% of alleles in individuals of South Asian 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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