Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002031318 | SCV002313578 | uncertain significance | Familial hemophagocytic lymphohistiocytosis 2 | 2024-09-30 | 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 373 of the PRF1 protein (p.Arg373Cys). This variant is present in population databases (rs374588624, gnomAD 0.01%). This missense change has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 17627755). ClinVar contains an entry for this variant (Variation ID: 1523906). Invitae Evidence 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 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. 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. |
Mayo Clinic Laboratories, |
RCV004793714 | SCV005411036 | uncertain significance | not provided | 2023-12-19 | criteria provided, single submitter | clinical testing | PM3_supporting |