Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002318140 | SCV000851321 | uncertain significance | Inborn genetic diseases | 2016-10-19 | criteria provided, single submitter | clinical testing | The p.R1053W variant (also known as c.3157C>T), located in coding exon 6 of the PCDH19 gene, results from a C to T substitution at nucleotide position 3157. The arginine at codon 1053 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV001216154 | SCV001387933 | uncertain significance | Developmental and epileptic encephalopathy, 9 | 2023-08-10 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 589955). This variant has not been reported in the literature in individuals affected with PCDH19-related conditions. This variant is present in population databases (rs774986147, gnomAD 0.005%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1053 of the PCDH19 protein (p.Arg1053Trp). |