Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001039596 | SCV001203131 | uncertain significance | Norman-Roberts syndrome; Familial temporal lobe epilepsy 7 | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 3453 of the RELN protein (p.Arg3453Gln). This variant is present in population databases (rs200731411, gnomAD 0.005%). This missense change has been observed in individual(s) with RELN-related conditions (PMID: 33004838). ClinVar contains an entry for this variant (Variation ID: 838111). 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 | RCV002553060 | SCV003752144 | uncertain significance | Inborn genetic diseases | 2022-08-17 | criteria provided, single submitter | clinical testing | The c.10358G>A (p.R3453Q) alteration is located in exon 65 (coding exon 65) of the RELN gene. This alteration results from a G to A substitution at nucleotide position 10358, causing the arginine (R) at amino acid position 3453 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |