ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.3475A>G (p.Asn1159Asp)

gnomAD frequency: 0.00001  dbSNP: rs774549370
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000658126 SCV000779897 uncertain significance not provided 2018-05-17 criteria provided, single submitter clinical testing The N1159D variant in the RPGRIP1L gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N1159D variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The N1159D variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret N1159D as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001212611 SCV001384200 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2019-09-24 criteria provided, single submitter clinical testing 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RPGRIP1L-related conditions. ClinVar contains an entry for this variant (Variation ID: 546275). This variant is present in population databases (rs774549370, ExAC 0.002%). This sequence change replaces asparagine with aspartic acid at codon 1159 of the RPGRIP1L protein (p.Asn1159Asp). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and aspartic acid.

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.