ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.1480T>G (p.Ser494Ala)

gnomAD frequency: 0.00003  dbSNP: rs202201818
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484670 SCV000574345 uncertain significance not provided 2024-02-09 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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
Fulgent Genetics, Fulgent Genetics RCV002489181 SCV002778161 uncertain significance Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 2022-03-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002525976 SCV003487632 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-10-04 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 494 of the RPGRIP1L protein (p.Ser494Ala). This variant is present in population databases (rs202201818, gnomAD 0.01%). 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: 424528). 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.
Revvity Omics, Revvity RCV000484670 SCV003811886 uncertain significance not provided 2021-06-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV003362799 SCV004055439 uncertain significance Inborn genetic diseases 2023-08-08 criteria provided, single submitter clinical testing The c.1480T>G (p.S494A) alteration is located in exon 13 (coding exon 12) of the RPGRIP1L gene. This alteration results from a T to G substitution at nucleotide position 1480, causing the serine (S) at amino acid position 494 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001829390 SCV002085728 uncertain significance Familial aplasia of the vermis 2020-10-08 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004535535 SCV004737511 uncertain significance RPGRIP1L-related disorder 2024-01-30 no assertion criteria provided clinical testing The RPGRIP1L c.1480T>G variant is predicted to result in the amino acid substitution p.Ser494Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.015% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.