Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000988376 | SCV001138068 | pathogenic | Familial hemophagocytic lymphohistiocytosis 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000988376 | SCV001199702 | pathogenic | Familial hemophagocytic lymphohistiocytosis 2 | 2023-12-02 | 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 54 of the PRF1 protein (p.Arg54Cys). This variant is present in population databases (rs200430442, gnomAD 0.01%). This missense change has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 14757862, 17266056, 21152410, 22437823). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 802583). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PRF1 protein function. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003473536 | SCV004204188 | pathogenic | Aplastic anemia | 2023-10-11 | criteria provided, single submitter | clinical testing |