Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
RCV001196513 | SCV001367121 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy 1 | 2020-03-09 | criteria provided, single submitter | clinical testing | This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,BP4. |
Invitae | RCV003114251 | SCV003787871 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 395 of the CHRNA4 protein (p.Thr395Met). 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. This variant has not been reported in the literature in individuals affected with CHRNA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 98307). 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 CHRNA4 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. |
Psychiatry Genetics Yale University | RCV000084597 | SCV000116733 | not provided | Tobacco use disorder | no assertion provided | not provided |