ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.1289A>T (p.Gln430Leu)

gnomAD frequency: 0.00001  dbSNP: rs770032567
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001053025 SCV001217267 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-10-18 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 430 of the RPGRIP1L protein (p.Gln430Leu). This variant is present in population databases (rs770032567, gnomAD 0.004%). 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: 849131). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RPGRIP1L 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.
GeneDx RCV001772265 SCV001994664 uncertain significance not provided 2019-03-22 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002497412 SCV002807017 uncertain significance Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 2022-02-17 criteria provided, single submitter clinical testing
Natera, Inc. RCV001827333 SCV002085735 uncertain significance Familial aplasia of the vermis 2021-08-19 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004733130 SCV005351343 uncertain significance RPGRIP1L-related disorder 2024-05-07 no assertion criteria provided clinical testing The RPGRIP1L c.1289A>T variant is predicted to result in the amino acid substitution p.Gln430Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0036% 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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