Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003644739 | SCV004476612 | uncertain significance | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2023-04-12 | 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 expected to disrupt PIGA protein function. This variant has not been reported in the literature in individuals affected with PIGA-related conditions. This variant is present in population databases (rs139991272, gnomAD 0.008%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 303 of the PIGA protein (p.His303Arg). |