Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000014718 | SCV001533915 | likely pathogenic | Familial hemophagocytic lymphohistiocytosis 2 | 2023-09-04 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs28933376, gnomAD 0.009%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 435 of the PRF1 protein (p.Thr435Met). 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects PRF1 function (PMID: 18927437, 19487666). ClinVar contains an entry for this variant (Variation ID: 13717). This missense change has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 12599189, 25233452, 32542393). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. |
Genome Diagnostics Laboratory, |
RCV002260966 | SCV002542765 | likely pathogenic | Autoinflammatory syndrome | 2022-02-22 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003473103 | SCV004204178 | likely pathogenic | Aplastic anemia | 2023-10-26 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000014718 | SCV000034973 | pathogenic | Familial hemophagocytic lymphohistiocytosis 2 | 2003-03-15 | no assertion criteria provided | literature only |