ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.3826C>T (p.Arg1276Ter) (rs199474742)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492784 SCV000581268 pathogenic Hereditary cancer-predisposing syndrome 2015-03-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Center for Human Genetics, Inc RCV000227284 SCV000782000 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000227284 SCV000692350 pathogenic Neurofibromatosis, type 1 2016-03-09 no assertion criteria provided clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000238903 SCV000296990 pathogenic not provided 2015-10-20 criteria provided, single submitter clinical testing
GeneDx RCV000238903 SCV000568607 pathogenic not provided 2018-12-03 criteria provided, single submitter clinical testing This variant is denoted NF1 c.3826C>T at the cDNA level and p.Arg1276Ter (R1276X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in numerous individuals meeting clinical diagnostic criteria for Neurofibromatosis Type 1 (Messiaen 2000, Kluwe 2002, Bausch 2007, Griffiths 2007, Valero 2011, Ko 2013, Paria 2014, Duat Rodr?guez 2015). This variant is considered pathogenic.
Genetic Services Laboratory, University of Chicago RCV000227284 SCV000595980 pathogenic Neurofibromatosis, type 1 2016-04-09 criteria provided, single submitter clinical testing
Invitae RCV000227284 SCV000284446 pathogenic Neurofibromatosis, type 1 2018-12-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1276*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs199474742, ExAC 0.001%). This variant has been reported in many individuals affected with neurofibromatosis type 1 (PMID: 7655472, 11857752, 26056819, 23668869, 16944272, 10862084, 10712197). ClinVar contains an entry for this variant (Variation ID: 237556). Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). For these reasons, this variant has been classified as Pathogenic.

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.