ClinVar Miner

Submissions for variant NM_004974.4(KCNA2):c.1220C>G (p.Pro407Arg)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001379013 SCV001576727 likely pathogenic Epileptic encephalopathy, early infantile, 32 2020-10-09 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 407 of the KCNA2 protein (p.Pro407Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with KCNA2-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 expected to disrupt KCNA2 protein function. This variant disrupts the p.Pro407 amino acid residue in KCNA2. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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