Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000188398 | SCV000242010 | pathogenic | not provided | 2022-08-16 | criteria provided, single submitter | clinical testing | Reported previously in a mother and daughter with seizures, developmental delay/learning disability, and/or autism (Smith et al., 2018); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32425876, 31928905, 29377098, 31618753) |
| Invitae | RCV001857629 | SCV002233365 | pathogenic | Developmental and epileptic encephalopathy, 9 | 2022-12-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 206361). This premature translational stop signal has been observed in individuals with PCDH19-related conditions (PMID: 29377098, 31618753, 32425876). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr166*) in the PCDH19 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCDH19 are known to be pathogenic (PMID: 21053371). |
| Victorian Clinical Genetics Services, |
RCV001857629 | SCV003921968 | pathogenic | Developmental and epileptic encephalopathy, 9 | 2020-11-05 | criteria provided, single submitter | clinical testing | 0102 - Loss of function is a known mechanism of disease in this gene and is associated with early infantile epileptic encephalopathy 9 (MIM#300088). (I) 0110 - This gene is associated with X-linked dominant disease. Heterozygous females are most often affected, however mosaic males have also been reported. (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) 0302 - Variant is absent in gnomAD (both v2 and v3); however, a different nucleotide change resulting in the same protein change is present in gnomAD (v2) <0.001 for a dominant condition (1 heterozygote, 0 homozygotes, 0 hemizygotes). (SP) 0701 - Other variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. More than a hundred other NMD-predicted variants have previously been reported as pathogenic in patients with early infantile epileptic encephalopathy 9 (MIM#300088) (ClinVar). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. The variant has previously been reported in patients with early infantile epileptic encephalopathy 9 (MIM#300088), including a heterozygous female where the variant was inherited from an affected mother, and a mosaic male in whom the variant was shown to be <i>de novo</i> (ClinVar, PMID: 29377098, PMID: 32425876). (SP) 1102 - Strong phenotype match for this individual. (SP) 1203 - This variant has been shown to be <i>de novo</i> in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |