ClinVar Miner

Submissions for variant NM_001184880.2(PCDH19):c.1129G>C (p.Asp377His)

dbSNP: rs1928407149
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001063090 SCV001227924 pathogenic Developmental and epileptic encephalopathy, 9 2023-08-14 criteria provided, single submitter clinical testing This variant disrupts the p.Asp377 amino acid residue in PCDH19. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22848613, 29933521). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 857424). This missense change has been observed in individual(s) with clinical features of early infantile epileptic encephalopathy (PMID: 20713952, 21777234). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 377 of the PCDH19 protein (p.Asp377His). For these reasons, this variant has been classified as Pathogenic.

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