Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002238609 | SCV002511682 | uncertain significance | not specified | 2025-05-30 | criteria provided, single submitter | clinical testing | Variant summary: CLCN2 c.2156C>T (p.Ser719Leu) results in a non-conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The variant allele was found at a frequency of 2.7e-05 in 1606120 control chromosomes (i.e. in 44 carriers) in the gnomAD database (v4.1 dataset). The occurrence in several carriers suggests that the variant is not causal for a dominant, high penetrance, early onset disease phenotype. The variant, c.2156C>T, has been observed in a proband affected with childhood absence epilepsy who inherited it from an apparently healthy carrier mother. EEG studies performed on the mother showed bursts of phantom sharps and waves during hyperventilation, so the possibility of a subclinical presentation in the mother cannot be excluded based on the reported findings (Combi_2009). This report has since been cited by others (Wei_2017). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 1683303). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Fulgent Genetics, |
RCV002487039 | SCV002776681 | uncertain significance | Epilepsy, idiopathic generalized, susceptibility to, 11; Familial hyperaldosteronism type II; Leukoencephalopathy with mild cerebellar ataxia and white matter edema | 2022-05-18 | criteria provided, single submitter | clinical testing |