Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000653137 | SCV000775013 | pathogenic | Developmental and epileptic encephalopathy, 32 | 2024-06-24 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 406 of the KCNA2 protein (p.Val406Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of KCNA2-related conditions (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 542666). 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 with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
Institute of Human Genetics, |
RCV000653137 | SCV004027832 | likely pathogenic | Developmental and epileptic encephalopathy, 32 | 2023-05-05 | criteria provided, single submitter | clinical testing | Criteria applied: PM1,PM2_SUP,PP3, PS2_MOD |