Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000815155 | SCV000955601 | uncertain significance | Developmental and epileptic encephalopathy, 9 | 2022-11-08 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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. 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. ClinVar contains an entry for this variant (Variation ID: 658348). This variant has not been reported in the literature in individuals affected with PCDH19-related conditions. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1119 of the PCDH19 protein (p.Glu1119Lys). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002265895 | SCV002548160 | uncertain significance | not specified | 2022-05-19 | criteria provided, single submitter | clinical testing | Variant summary: PCDH19 c.3355G>A (p.Glu1119Lys) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 181638 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3355G>A has been reported in the literature as a Pathogenic/Likely Pathogenic variant in at-least one family or at-least one individual analyzed as part of the Cincinnati Clinical Exome Pipeline Analysis Suite (CCEPAS) without specifying the evidence rationale underlying the reported outcome (example, Valencia_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Developmental And Epileptic Encephalopathy, 9. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV003279098 | SCV003963375 | uncertain significance | Inborn genetic diseases | 2023-03-27 | criteria provided, single submitter | clinical testing | The c.3355G>A (p.E1119K) alteration is located in exon 6 (coding exon 6) of the PCDH19 gene. This alteration results from a G to A substitution at nucleotide position 3355, causing the glutamic acid (E) at amino acid position 1119 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |