ClinVar Miner

Submissions for variant NM_001083116.3(PRF1):c.148G>C (p.Val50Leu)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003062266 SCV003441621 uncertain significance Familial hemophagocytic lymphohistiocytosis 2 2022-06-09 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 50 of the PRF1 protein (p.Val50Leu). This variant is present in population databases (rs776299562, gnomAD 0.06%). This missense change has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 27033761). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Val50 amino acid residue in PRF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11179007, 14757862, 15755897, 16374518, 18190960, 19487666). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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