ClinVar Miner

Submissions for variant NM_001083116.3(PRF1):c.1070G>A (p.Arg357Gln)

gnomAD frequency: 0.00027  dbSNP: rs140787739
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000820406 SCV000961117 uncertain significance Familial hemophagocytic lymphohistiocytosis 2 2022-10-31 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 357 of the PRF1 protein (p.Arg357Gln). This variant is present in population databases (rs140787739, gnomAD 0.1%). 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: 662697). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PRF1 protein function. 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.
Illumina Laboratory Services, Illumina RCV000820406 SCV001261254 uncertain significance Familial hemophagocytic lymphohistiocytosis 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002261229 SCV002542759 uncertain significance Autoinflammatory syndrome 2021-12-20 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002478919 SCV002799707 uncertain significance Aplastic anemia; Familial hemophagocytic lymphohistiocytosis 2; Lymphoma, non-Hodgkin, familial 2022-03-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV002537468 SCV003633495 likely benign Inborn genetic diseases 2022-05-06 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity RCV003130075 SCV003809863 uncertain significance not provided 2019-02-01 criteria provided, single submitter clinical testing

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