Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000004232 | SCV003238894 | uncertain significance | Glutamate formiminotransferase deficiency | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 135 of the FTCD protein (p.Arg135Cys). 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 missense change has been observed in individual(s) with glutamate formiminotransferase deficiency (PMID: 12815595). This variant is also known as c.457C>T. ClinVar contains an entry for this variant (Variation ID: 4017). 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 FTCD protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects FTCD function (PMID: 12815595). 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. |
| OMIM | RCV000004232 | SCV000024398 | pathogenic | Glutamate formiminotransferase deficiency | 2003-07-01 | no assertion criteria provided | literature only |