Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001053951 | SCV001218238 | uncertain significance | Developmental and epileptic encephalopathy, 9 | 2023-09-25 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 834 of the PCDH19 protein (p.Asn834Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PCDH19-related conditions. ClinVar contains an entry for this variant (Variation ID: 849896). 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 not expected to disrupt PCDH19 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
New York Genome Center | RCV001053951 | SCV001622989 | uncertain significance | Developmental and epileptic encephalopathy, 9 | 2020-07-02 | criteria provided, single submitter | clinical testing | The p.Asn834Ser missense variant identified in the PCDH19 gene has 0.0001325 allele frequency in the gnomAD database (14 out of 105,671 alleles, 2 hemizygotes) indicating it is a rare allele in the populations represented in gnomAD database. The affected residue is evolutionarily conserved. In silico tools provide conflicting interpretations about potential pathogenicy of this variant. Based on the available evidence, the p.Asn834Ser variant in PCDH19 is assessed as a variant of uncertain significance. |
Gene |
RCV001585953 | SCV001820077 | likely benign | not provided | 2020-10-26 | criteria provided, single submitter | clinical testing |