Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV003466860 | SCV004206476 | likely pathogenic | Aplastic anemia | 2023-07-06 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000014714 | SCV004294731 | pathogenic | Familial hemophagocytic lymphohistiocytosis 2 | 2023-09-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PRF1 function (PMID: 15755897). 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. ClinVar contains an entry for this variant (Variation ID: 13714). This missense change has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 10583959, 12060139, 17627755; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs104894182, gnomAD 0.004%). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 279 of the PRF1 protein (p.Cys279Tyr). |
OMIM | RCV000014714 | SCV000034969 | pathogenic | Familial hemophagocytic lymphohistiocytosis 2 | 1999-12-03 | no assertion criteria provided | literature only |