Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188378 | SCV000241990 | pathogenic | not provided | 2019-10-14 | criteria provided, single submitter | clinical testing | Previously reported to segregate with epilepsy in several females from a single family who had febrile, generalized, and/or focal seizures, one of whom also had cognitive delay (Depienne et al., 2011); 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 in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23334464, 22267240, 25525159, 21053371, 27179713, 23712037, 22633638, 29377098) |
Athena Diagnostics Inc | RCV000188378 | SCV000614416 | pathogenic | not provided | 2017-02-16 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002426910 | SCV002744083 | pathogenic | Inborn genetic diseases | 2019-06-14 | criteria provided, single submitter | clinical testing | The p.R886* pathogenic mutation (also known as c.2656C>T), located in coding exon 4 of the PCDH19 gene, results from a C to T substitution at nucleotide position 2656. This changes the amino acid from an arginine to a stop codon within coding exon 4. This variant has been reported in 5 females with seizures, including one family with 4 affected women (Depienne C et al. Hum. Mutat., 2011 Jan;32:E1959-75; Smith L et al. Epilepsia, 2018 03;59:679-689). 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. |
Invitae | RCV002517880 | SCV002943715 | pathogenic | Developmental and epileptic encephalopathy, 9 | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg886*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with generalized epilepsy with febrile seizures plus (PMID: 21053371). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 206341). For these reasons, this variant has been classified as Pathogenic. |