Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000188352 | SCV000241964 | pathogenic | not provided | 2018-04-17 | criteria provided, single submitter | clinical testing | The R207X variant in the PCDH19 gene has been reported previously as an apparently de novo variant in a patient with generalized seizures presenting at 15 months of age, language delay, and behavior problems (Smith et al., 2018). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R207X variant is not observed in large population cohorts (Lek et al., 2016). Additionally, R207X has been observed as a de novo variant with confirmed parentage in a patient with focal epilepsy and epileptic encephalopathy previously tested at GeneDx. We interpret R207X as a pathogenic variant. |
| Victorian Clinical Genetics Services, |
RCV002272165 | SCV002557507 | pathogenic | Developmental and epileptic encephalopathy, 9 | 2022-09-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with developmental and epileptic encephalopathy 9 (MIM#300088). (I) 0110 - This gene is associated with X-linked disease. Heterozygous females and mosaic males are affected, however hemizygous males do not present with symptoms (PMID: 28669061). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been observed as a de novo event in two individuals with seizures (ClinVar, PMIDs: 29655203, 29377098). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1204 - This variant has been shown to be de novo in the proband (parental status not tested but assumed) (by segregation analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |