Total submissions: 3
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. |
Ce |
RCV003457811 | SCV004185478 | likely benign | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | RELN: BS1:Supporting |