Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics, |
RCV003994533 | SCV003921039 | likely pathogenic | KCNA3-associated developmental and epileptic encephalopathy | 2023-02-14 | criteria provided, single submitter | research | This variant was identified as de novo (maternity and paternity confirmed). Criteria applied: PS3, PS2_MOD, PM2_SUP, PP3 |
| Victorian Clinical Genetics Services, |
RCV004786900 | SCV005398236 | likely pathogenic | Neurodevelopmental disorder | 2024-09-22 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established. This gene is associated with neurodevelopmental disorder, MONDO:0700092, KCNA3-related. (I) 0107 - This gene is associated with autosomal dominant disease (personal communication). (I) 0200 - Variant is predicted to result in a missense amino acid change from threonine to isoleucine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0602 - Variant is located in a hotspot region or cluster of pathogenic variants from residues 431 to 478 (DECIPHER, Personal communications). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0802 - This variant has moderate previous evidence of pathogenicity in an unrelated individual. This variant has been identified in a de novo heterozygous individual with developmental and epileptic encephalopathy (Personal communications). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1002 - This variant has moderate functional evidence supporting abnormal protein function. This variant causes absent Kv1.3 channel current, and when co-transfected it suppresses currents carried by wild-type Kv1.3 subunits (Personal communications). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |