Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002933279 | SCV003265800 | pathogenic | Familial hemophagocytic lymphohistiocytosis 2 | 2024-03-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser150*) in the PRF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PRF1 are known to be pathogenic (PMID: 1156555, 16860143). This variant is present in population databases (rs773267292, gnomAD 0.04%). This premature translational stop signal has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 14757862). This variant is also known as S150X. ClinVar contains an entry for this variant (Variation ID: 2055336). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003331403 | SCV004038415 | pathogenic | Familial hemophagocytic lymphohistiocytosis | 2023-08-08 | criteria provided, single submitter | clinical testing | Variant summary: PRF1 c.449C>A (p.Ser150X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2e-05 in 251434 control chromosomes (gnomAD). c.449C>A has been reported in the literature in individuals affected with Familial Hemophagocytic Lymphohistiocytosis (Molleran_2004, Risma_2005). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 14757862, 16374518, 32696691). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV003475454 | SCV004204194 | pathogenic | Aplastic anemia | 2024-01-16 | criteria provided, single submitter | clinical testing |