ClinVar Miner

Submissions for variant NM_018718.3(CEP41):c.1081T>C (p.Ser361Pro)

gnomAD frequency: 0.00001  dbSNP: rs587780311
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000116676 SCV000150640 uncertain significance not provided 2013-07-03 criteria provided, single submitter clinical testing
GeneDx RCV000116676 SCV000570439 uncertain significance not provided 2016-05-20 criteria provided, single submitter clinical testing The S361P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S361P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV003642869 SCV004450291 uncertain significance Joubert syndrome 15 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 361 of the CEP41 protein (p.Ser361Pro). This variant is present in population databases (rs587780311, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CEP41-related conditions. ClinVar contains an entry for this variant (Variation ID: 128704). 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 CEP41 protein function with a negative predictive value of 80%. 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.
Breakthrough Genomics, Breakthrough Genomics RCV000116676 SCV005195661 uncertain significance not provided criteria provided, single submitter not provided

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.