Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000826212 | SCV000967778 | likely pathogenic | Familial hemophagocytic lymphohistiocytosis | 2019-01-04 | criteria provided, single submitter | clinical testing | The p.Gln86X variant in PRF1 has not been previously reported in individuals wit h hemophagocytic lymphohistiocytosis (HLH) and was absent from large population studies. This nonsense variant leads to a premature termination codon at positio n 86, which is predicted to lead to a truncated or absent protein. Loss of funct ion of the PRF1 gene is an established disease mechanism in autosomal recessive HLH. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely p athogenic for autosomal recessive HLH. ACMG/AMP Criteria applied: PVS1, PM2. |