Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004700235 | SCV005202929 | uncertain significance | not specified | 2024-07-23 | criteria provided, single submitter | clinical testing | Variant summary: PRF1 c.1163G>T (p.Ser388Ile) results in a non-conservative amino acid change located in the Perforin-1, C2 domain (IPR037300) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 246806 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1163G>T has been reported in the literature in the presumed compound heterozygous state with the p.Ala91Val variant (Likely Benign by our laboratory) in at least 1 individual affected with clinical features of Familial Hemophagocytic Lymphohistiocytosis and loss of detectable perforin protein (example, Solomou_2007). These report(s) do not provide unequivocal conclusions about association of the variant with Familial Hemophagocytic Lymphohistiocytosis. Cytolytic activity in patient cells was reduced vs. controls (example, Solomou_2007), however the impact of this variant alone could not be determined. The following publication has been ascertained in the context of this evaluation (PMID: 17311987). ClinVar contains an entry for this variant (Variation ID: 13719). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| OMIM | RCV000014722 | SCV000034977 | pathogenic | Aplastic anemia | 2007-06-15 | no assertion criteria provided | literature only |