ClinVar Miner

Submissions for variant NM_000742.4(CHRNA2):c.137C>T (p.Pro46Leu)

dbSNP: rs748345482
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001977287 SCV002259511 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 2021-04-11 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. This sequence change replaces proline with leucine at codon 46 of the CHRNA2 protein (p.Pro46Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs748345482, ExAC 0.01%). This variant has not been reported in the literature in individuals with CHRNA2-related conditions. 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 CHRNA2 protein function.
GeneDx RCV003222373 SCV003918245 uncertain significance not provided 2023-04-04 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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