Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001067235 | SCV001232282 | pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2022-07-12 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Asp452 amino acid residue in PIGA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31704190). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 860851). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 452 of the PIGA protein (p.Asp452Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of PIGA-congenital disorder of glycosylation (Invitae). In at least one individual the variant was observed to be de novo. |