Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000485682 | SCV000573086 | uncertain significance | not provided | 2017-02-16 | criteria provided, single submitter | clinical testing | The V431L variant in the CHRNB2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Adequate data is not available in large population cohorts to assess the frequency of this variant in publicly available databases; however, this variant has not been detected at a significant frequency in presumably healthy individuals tested at GeneDx. The V431L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret V431L as a variant of uncertain significance. |
Genomic Research Center, |
RCV000626232 | SCV000746879 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy 3 | 2020-05-03 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000485682 | SCV002544314 | uncertain significance | not provided | 2022-06-01 | criteria provided, single submitter | clinical testing | CHRNB2: PM2, PP2, PP3 |
Invitae | RCV003746526 | SCV004559164 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy | 2022-12-22 | criteria provided, single submitter | clinical testing | 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. 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 CHRNB2 protein function. ClinVar contains an entry for this variant (Variation ID: 423390). This variant has not been reported in the literature in individuals affected with CHRNB2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.04%). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 431 of the CHRNB2 protein (p.Val431Leu). |