Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001350410 | SCV001544809 | pathogenic | Developmental and epileptic encephalopathy, 9 | 2021-07-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 414 of the PCDH19 protein (p.Glu414Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of PCDH19-related conditions (PMID: 27527380, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1045922). 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 disrupts the p.Glu414 amino acid residue in PCDH19. Other variant(s) that disrupt this residue have been observed in individuals with PCDH19-related conditions (PMID: 20713952), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |