Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003628580 | SCV004452249 | likely pathogenic | Familial hemophagocytic lymphohistiocytosis 2 | 2023-04-08 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the C-terminus of the PRF1 protein. Other variant(s) that disrupt this region (p.Glu545Glyfs*41, p.Pro546Leufs*6, p.Met541Cysfs*71) have been observed in individuals with PRF1-related conditions (PMID: 14757862, 31664448). This suggests that this may be a clinically significant region of the protein. This variant has not been reported in the literature in individuals affected with PRF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the PRF1 gene (p.Tyr537Cysfs*48). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 19 amino acid(s) of the PRF1 protein and extend the protein by 28 additional amino acid residues. |