ClinVar Miner

Submissions for variant NM_001184880.2(PCDH19):c.1787A>G (p.Asp596Gly)

dbSNP: rs2147537831
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV002249121 SCV002517353 likely pathogenic Developmental and epileptic encephalopathy, 9 2022-05-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002249121 SCV003445760 pathogenic Developmental and epileptic encephalopathy, 9 2022-07-30 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 596 of the PCDH19 protein (p.Asp596Gly). ClinVar contains an entry for this variant (Variation ID: 1685394). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asp596 amino acid residue in PCDH19. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22946748, 23712037, 25891919). 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. This missense change has been observed in individuals with clinical features of epileptic encephalopathy with cerebellar atrophy (PMID: 25891919; Invitae).

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