Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000680065 | SCV000807505 | uncertain significance | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2017-09-01 | criteria provided, single submitter | clinical testing | Likely pathogenicity based on finding it once in our laboratory de novo in a 14-year-old male with epilepsy, global delays, weakness, poor coordination, hypotnia, failure to thrive, profound white matter atrophy |
| Invitae | RCV000680065 | SCV001510701 | pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2022-09-13 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 561081). This missense change has been observed in individual(s) with PIGA-related conditions (PMID: 25326635, 32220244, 33763700). In at least one individual the variant was observed to be de novo. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 81 of the PIGA protein (p.Arg81Cys). |