ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.1318C>T (p.Arg440Ter) (rs778405030)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000213237 SCV000274305 pathogenic Hereditary cancer-predisposing syndrome 2015-03-04 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 RCV000225855 SCV000781902 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762984 SCV000893429 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
GeneDx RCV000519956 SCV000616807 pathogenic not provided 2018-08-17 criteria provided, single submitter clinical testing The R440X nonsense variant in the NF1 gene has been previously reported in many individuals with neurofibromatosis type 1, and was found to be de novo in at least one individual (for examples, see Heim et al., 1995; Krkljus et al., 1998; Stewart et al., 2014; Hirbe et al., 2015). This 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 R440X to be pathogenic.
Invitae RCV000225855 SCV000284377 pathogenic Neurofibromatosis, type 1 2018-11-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg440*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs778405030, ExAC 0.01%). This variant has been reported in numerous individuals with neurofibromatosis type 1 (PMID: 7655472, 23668869, 16835897, 10862084, 10543400, 10712197, 24922668). ClinVar contains an entry for this variant (Variation ID: 230673). Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). For these reasons, this variant has been classified as Pathogenic.

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