Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002318268 | SCV000851569 | uncertain significance | Inborn genetic diseases | 2017-03-06 | criteria provided, single submitter | clinical testing | The p.I1146T variant (also known as c.3437T>C), located in coding exon 6 of the PCDH19 gene, results from a T to C substitution at nucleotide position 3437. The isoleucine at codon 1146 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001218532 | SCV001390418 | uncertain significance | Developmental and epileptic encephalopathy, 9 | 2023-06-20 | criteria provided, single submitter | clinical testing | 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: 590086). This variant has not been reported in the literature in individuals affected with PCDH19-related conditions. This variant is present in population databases (rs186554435, gnomAD 0.03%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1146 of the PCDH19 protein (p.Ile1146Thr). |