ClinVar Miner

Submissions for variant NM_001184880.2(PCDH19):c.634G>C (p.Asp212His) (rs796052806)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188356 SCV000241968 likely pathogenic not provided 2013-09-26 criteria provided, single submitter clinical testing This variant is denoted p.Asp212His (GAC>CAC): c.634 G>C in exon 1 of the PCDH19 gene (NM_001105243.1). The Asp212His 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 5,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution of a negatively charged Aspartic acid residue with a positively charged Histidine residue. Asp212His alters a highly conserved position at a Ca2+ binding site within the extracellular second cadherin repeat domain of the protocadherin 19 protein and other missense mutations in this domain have been published in associated with epilepsy (Depienne et al., 2011; Depienne et al., 2012). In addition, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, Asp212His is a strong candidate for a disease-causing mutation, although the possibility that it is a benign variant cannot be excluded. Somatic mosaicism for PCDH19 mutations have been reported previously (Terracciano et al., 2012; Dibbens et al., 2011). This variant has been seen apparently mosaic. The variant is found in EPILEPSY panel(s).

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