ClinVar Miner

Submissions for variant NM_001184880.2(PCDH19):c.1682C>G (p.Pro561Arg) (rs796052819)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188374 SCV000241986 pathogenic not provided 2014-03-17 criteria provided, single submitter clinical testing This variant is denoted p.Pro561Arg (CCG>CGG): c.1682 C>G in exon 1 of the PCDH19 gene (NM_001105243.1). The P561R missense mutation in the PCDH19 gene has been reported previously in association with epilepsy and mental retardation limited to females (EFMR) and was identified in two affected sisters and their unaffected father (Depienne et al.,2011). This mutation alters a highly conserved residue in the PCDH19 protein. Therefore, the presence of P561R is consistent with a diagnosis of a PCDH19-related disorder. The variant is found in EPILEPSY panel(s).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000188374 SCV000701651 uncertain significance not provided 2016-10-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000720392 SCV000851269 likely pathogenic History of neurodevelopmental disorder 2016-10-17 criteria provided, single submitter clinical testing The p.P561R variant (also known as c.1682C>G), located in coding exon 1 of the PCDH19 gene, results from a C to G substitution at nucleotide position 1682. The proline at codon 561 is replaced by arginine, an amino acid with dissimilar properties. This alteration was detected with paternal transmission in two female siblings who both had intellectual disability, microcephaly, and developed various seizure types, including generalized tonic-clonic, absence, partial, and tonic, before age one (Depienne C et al. Hum. Mutat., 2011 Jan;32:E1959-75). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6375 samples with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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