ClinVar Miner

Submissions for variant NM_005045.4(RELN):c.6170T>G (p.Leu2057Arg)

gnomAD frequency: 0.00006  dbSNP: rs138909076
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000803791 SCV000943677 uncertain significance Norman-Roberts syndrome; Familial temporal lobe epilepsy 7 2023-12-25 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2057 of the RELN protein (p.Leu2057Arg). This variant is present in population databases (rs138909076, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RELN-related conditions. ClinVar contains an entry for this variant (Variation ID: 648956). 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 RELN 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.
Ambry Genetics RCV002534766 SCV003747763 uncertain significance Inborn genetic diseases 2022-06-29 criteria provided, single submitter clinical testing Unlikely to be causative of RELN-related lateral temporal epilepsy (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen RCV003457811 SCV004185478 likely benign not provided 2023-11-01 criteria provided, single submitter clinical testing RELN: BS1:Supporting

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.