Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
RCV001199137 | SCV001370133 | uncertain significance | Familial temporal lobe epilepsy 7 | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PP3,PP4. |
Labcorp Genetics |
RCV001248020 | SCV001421479 | uncertain significance | Norman-Roberts syndrome; Familial temporal lobe epilepsy 7 | 2023-08-30 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with RELN-related conditions. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2423 of the RELN protein (p.Arg2423Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. ClinVar contains an entry for this variant (Variation ID: 932028). 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. 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. |