Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000526406 | SCV000640261 | uncertain significance | Developmental and epileptic encephalopathy, 9 | 2023-03-27 | 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. ClinVar contains an entry for this variant (Variation ID: 465298). This variant has not been reported in the literature in individuals affected with PCDH19-related conditions. 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 sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 752 of the PCDH19 protein (p.Lys752Arg). 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. |
Ambry Genetics | RCV002526131 | SCV003543492 | uncertain significance | Inborn genetic diseases | 2021-12-06 | criteria provided, single submitter | clinical testing | The c.2255A>G (p.K752R) alteration is located in exon 2 (coding exon 2) of the PCDH19 gene. This alteration results from a A to G substitution at nucleotide position 2255, causing the lysine (K) at amino acid position 752 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |