ClinVar Miner

Submissions for variant NM_001184880.2(PCDH19):c.1335C>A (p.Asp445Glu)

dbSNP: rs796052815
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188368 SCV000241980 likely pathogenic not provided 2013-03-15 criteria provided, single submitter clinical testing This variant is denoted p.Asp445Glu (GAC>GAA): c.1335 C>A in exon 1 of the PCDH19 gene (NM_001105243.1). The Asp445Glu missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project or among the various ethnic groups studied in the 1000 Genomes Project, indicating it is not a common benign variant in these populations. The amino acid substitution is conservative as both Aspartic acid and Glutamic acid are negatively charged, polar amino acid residues. However, Asp445Glu alters a highly conserved position in the fourth extracellular cadherin repeat domain of the protein and other missense mutations in this domain have been published in association with epilepsy (Dibbens et al., 2008; Specchio et al., 2011). In addition, multiple in-silico algorithms predict Asp445Glu may be damaging to the structure/function of the protein. Therefore, based on the currently available information, Asp445Glu is a strong candidate for a disease-causing mutation, although the possibility that it is a benign variant cannot be excluded. The variant is found in EPILEPSY panel(s).
Neurogenetics Research Program, University of Adelaide RCV001199422 SCV001147056 likely pathogenic Glycine encephalopathy; Developmental and epileptic encephalopathy, 9 2019-12-20 no assertion criteria provided research

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