Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000685792 | SCV000813290 | pathogenic | Developmental and epileptic encephalopathy, 9 | 2020-06-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr306*) in the PCDH19 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported as mosaic and de novo in a male affected with PCDH19-related epilepsy (PMID: 26765483). Loss-of-function variants in PCDH19 are known to be pathogenic (PMID: 21053371). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002369822 | SCV002687045 | pathogenic | Inborn genetic diseases | 2019-01-24 | criteria provided, single submitter | clinical testing | The p.Y306* pathogenic mutation (also known as c.918C>G), located in coding exon 1 of the PCDH19 gene, results from a C to G substitution at nucleotide position 918. This changes the amino acid from a tyrosine to a stop codon within coding exon 1. In one study, this mutation was detected as a mosaic occurrence in a male with afebrile seizures and an abnormal EEG (Terracciano A et al. Epilepsia, 2016 Mar;57:e51-5). In another study, this mutation was detected as paternally inherited in a female with generalized tonic-clonic seizures and an abnormal EEG (Tan Y et al. BMC Med. Genet., 2018 Jun;19:92). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |