Submissions for variant NM_001184880.2(PCDH19):c.1211C>T (p.Thr404Ile)

dbSNP: rs2147539327

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001956170	SCV002239452	pathogenic	Developmental and epileptic encephalopathy, 9	2021-03-28	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PCDH19 protein function. This variant has been observed in individual(s) with PCDH19-related conditions (PMID: 20713952). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 404 of the PCDH19 protein (p.Thr404Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine.
Department of Developmental Neurology, Medical University of Gdańsk	RCV001956170	SCV004100844	not provided	Developmental and epileptic encephalopathy, 9		no assertion provided	phenotyping only