Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001931453 | SCV002203530 | uncertain significance | Norman-Roberts syndrome; Familial temporal lobe epilepsy 7 | 2024-02-17 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 1166 of the RELN protein (p.His1166Tyr). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 1430330). 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 | RCV004041944 | SCV004939000 | uncertain significance | Inborn genetic diseases | 2023-10-17 | criteria provided, single submitter | clinical testing | The c.3496C>T (p.H1166Y) alteration is located in exon 25 (coding exon 25) of the RELN gene. This alteration results from a C to T substitution at nucleotide position 3496, causing the histidine (H) at amino acid position 1166 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |