ClinVar Miner

Submissions for variant NM_001083116.3(PRF1):c.529C>T (p.Arg177Cys)

gnomAD frequency: 0.00009  dbSNP: rs201468340
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001035779 SCV001199114 uncertain significance Familial hemophagocytic lymphohistiocytosis 2 2022-08-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 177 of the PRF1 protein (p.Arg177Cys). This variant is present in population databases (rs201468340, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PRF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 834984). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genetic Services Laboratory, University of Chicago RCV001819739 SCV002065289 uncertain significance not specified 2021-05-19 criteria provided, single submitter clinical testing DNA sequence analysis of the PRF1 gene demonstrated a sequence change, c.529C>T, in exon 2 that results in an amino acid change, p.Arg177Cys. This sequence change has been described in the gnomAD database with a frequency of 0.016% in the European (non-Finnish) subpopulation (dbSNP rs201468340). The p.Arg177Cys change affects a moderately conserved amino acid residue located in a domain of the PRF1 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg177Cys substitution. This sequence change has been previously described in two patients with anaplastic large cell lymphoma (PMID: 24309606, 17477373). Due to the lack of sufficient evidences, the clinical significance of the p.Arg177Cys change remains unknown at this time.
Fulgent Genetics, Fulgent Genetics RCV002479234 SCV002779279 uncertain significance Aplastic anemia; Familial hemophagocytic lymphohistiocytosis 2; Lymphoma, non-Hodgkin, familial 2022-04-18 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.