Submissions for variant NM_001184880.2(PCDH19):c.790G>T (p.Asp264Tyr) (rs587784300)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000147085	SCV000194437	uncertain significance	Early infantile epileptic encephalopathy 9	2013-10-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000490161	SCV000577673	likely pathogenic	not provided	2017-07-17	criteria provided, single submitter	clinical testing	A variant that is likely pathogenic has been identified in the PCDH19 gene. The D264Y variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. A different missense substitution at the same position (D264H) has been identified de novo in a female with PCDH19-gene related epilepsy (Marini et al., 2012). The D264Y variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D264Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.