ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.5839C>T (p.Arg1947Ter) (rs137854552)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000000371 SCV000260568 pathogenic Neurofibromatosis, type 1 2019-11-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1947*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported as a recurrent variant observed in many individuals affected with neurofibromatosis type 1 (PMID: 2114220, 7649559, 7903661, 8069310, 8385067, 10076878) including at least one de novo observation (Invitae). This variant is also known as 1087C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 343). Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000418287 SCV000521066 pathogenic not provided 2018-11-28 criteria provided, single submitter clinical testing The R1947X nonsense variant in the NF1 gene has been frequently reported in association with neurofibromatosis type 1 (Cawthon et al., 1990; Klose et al., 1999; Hutter et al., 2016). The R1947X variant was not observed in large population cohorts (Lek et al., 2016). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Based on currently available evidence, we consider R1947X to be pathogenic.
Ambry Genetics RCV000492774 SCV000581242 pathogenic Hereditary cancer-predisposing syndrome 2014-11-04 criteria provided, single submitter clinical testing The p.R1968* pathogenic mutation (also known as c.5902C>T) located in coding exon 40 of the NF1 gene, results from a C to T substitution at nucleotide position 5902. This changes the amino acid from an arginine to a stop codon within coding exon 40. This pathogenic mutation has been described as a recurring mutation in individuals with neurofibromatosis type 1 (Ars E et al. J. Med. Genet. 2003; 40:e82, Fahsold R et al. Am. J. Hum. Genet. 2000; 66:790-818). In addtition, it is located in a mutational hotspot of CpG dinucloetide repeats and methylated site of the gene (Andrews JD et al. Hum. Mol. Genet. 1996, 5:503-7). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). This pathogenic mutation is also known as p.R1947* (c.5839C>T) in the literature.
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000000371 SCV000693463 pathogenic Neurofibromatosis, type 1 2017-08-10 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000418287 SCV000842894 pathogenic not provided 2018-02-07 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762995 SCV000893440 pathogenic Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2018-10-31 criteria provided, single submitter clinical testing
The Laboratory of Genetics and Metabolism, Hunan Children’s Hospital RCV001009602 SCV001169703 pathogenic Neurofibromatosis, type 1; Tibial pseudoarthrosis 2018-11-10 criteria provided, single submitter research
Medical Genetics, University of Parma RCV000000371 SCV001218924 pathogenic Neurofibromatosis, type 1 2019-12-20 criteria provided, single submitter clinical testing
OMIM RCV000000371 SCV000020515 pathogenic Neurofibromatosis, type 1 2000-01-01 no assertion criteria provided literature only
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000000371 SCV000692361 pathogenic Neurofibromatosis, type 1 2017-03-03 no assertion criteria provided clinical testing

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