ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.1381C>T (p.Arg461Ter) (rs878853865)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229618 SCV000284378 pathogenic Neurofibromatosis, type 1 2019-12-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg461*) 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 in several individuals affected with neurofibromatosis type 1 (PMID: 10712197, 16479075, 23668869, 16944272, 15146469, 16835897, 10862084, 16941471, 24789688). ClinVar contains an entry for this variant (Variation ID: 237514). 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 RCV000255390 SCV000322350 pathogenic not provided 2018-12-10 criteria provided, single submitter clinical testing The R461X pathogenic variant in the NF1 gene has been reported previously in an individual with a clinical diagnosis of neurofibromatosis type 1 (Fahsold et al., 2000). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R461X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R461X as a pathogenic variant.
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000229618 SCV000537731 pathogenic Neurofibromatosis, type 1 2015-05-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000492771 SCV000581288 pathogenic Hereditary cancer-predisposing syndrome 2015-08-20 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000255390 SCV000885843 pathogenic not provided 2017-10-27 criteria provided, single submitter clinical testing The NF1 c.1381C>T; p.Arg461Ter variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to non-sense mediated decay. The variant is listed in the ClinVar database (Variation ID: 237514) and has been identified in several individuals with neurofibromatosis type 1 (NF1) (see link below and Fahsold 2000). Considering available information, this variant is classified as pathogenic. References: Link to LOVD NF1 Database for p.Arg461Ter: Fahsold R et al. Minor lesion mutational spectrum of the entire NF1 gene does not explain its high mutability but points to a functional domain upstream of the GAP-related domain. Am J Hum Genet. 2000 66(3):790-818.
Medical Genetics, University of Parma RCV000229618 SCV001218915 pathogenic Neurofibromatosis, type 1 2019-12-20 criteria provided, single submitter clinical testing

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