Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001061919 | SCV001226683 | uncertain significance | Developmental and epileptic encephalopathy, 9 | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 853 of the PCDH19 protein (p.Phe853Leu). This variant is not present in population databases (gnomAD no frequency). 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: 856452). 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 with a negative predictive value of 95%. 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. |
Revvity Omics, |
RCV001061919 | SCV003814745 | uncertain significance | Developmental and epileptic encephalopathy, 9 | 2021-06-17 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003945795 | SCV004762932 | uncertain significance | PCDH19-related condition | 2024-02-09 | criteria provided, single submitter | clinical testing | The PCDH19 c.2559C>G variant is predicted to result in the amino acid substitution p.Phe853Leu. To our knowledge, this variant has not been reported in the literature or in gnomAD v2; however, it has been observed in four females (XX) and one male (XY) from over 500,000 individuals tested for the X chromosome in gnomAD v4, indicating this variant is rare. This variant is currently classified as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/856452/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |