ClinVar Miner

Submissions for variant NM_000742.4(CHRNA2):c.835A>G (p.Ile279Val)

gnomAD frequency: 0.00001  dbSNP: rs1812595253
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001577807 SCV001805264 uncertain significance not provided 2018-12-24 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV003746593 SCV004517680 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 2023-08-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 279 of the CHRNA2 protein (p.Ile279Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHRNA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1209215). 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 expected to disrupt CHRNA2 protein function. This variant disrupts the p.Ile279Asn amino acid residue in CHRNA2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16826524). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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