ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.6709C>T (p.Arg2237Ter) (rs876658541)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223234 SCV000273924 pathogenic Hereditary cancer-predisposing syndrome 2015-01-08 criteria provided, single submitter clinical testing ​Thep.R2258*pathogenic mutation (also known as c.6772C>T, p.R2237X, and c.6709C>T)<span style="font-size:12.7272720336914px">located in coding exon 45 of theNF1<span style="font-size:12.7272720336914px">gene, results from a C to T substitution at nucleotide position 6772. This changes the amino acid from an arginine to a stop codon within coding exon 45. This alteration was first described in three unrelated individuals who all met NIH diagnostic criteria forneurofibromatosis type 1 (NF1) (Fahsold R et al.Am J Hum Genet.2000;66(3):790-818). This alteration is a recurring mutation due to being located in a CpG dinucleotide. 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).
Invitae RCV000461033 SCV000541996 pathogenic Neurofibromatosis, type 1 2019-11-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2237*) 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 observed in individual(s) with neurofibromatosis type 1 (PMID: 10712197, 12552569, 23913538, 16479075, 10862084, 26962827). This variant is also known as R2258X in the literature. ClinVar contains an entry for this variant (Variation ID: 230389). 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 RCV000578739 SCV000680725 pathogenic not provided 2018-12-20 criteria provided, single submitter clinical testing The R2237X nonsense variant in the NF1 gene has been reported previously in association with neurofibromatosis type 1 (Fahsold et al., 2000; Jeong et al., 2006). It has also been observed apparently de novo in at least one patient previously tested at GeneDx. The R2237X variant is 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.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000461033 SCV000782084 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Mendelics RCV000461033 SCV001140392 pathogenic Neurofibromatosis, type 1 2019-05-28 criteria provided, single submitter clinical testing
The Laboratory of Genetics and Metabolism, Hunan Children’s Hospital RCV001009581 SCV001169682 pathogenic Neurofibromatosis, type 1; Tibial pseudoarthrosis 2018-11-10 criteria provided, single submitter research
Medical Genetics, University of Parma RCV000461033 SCV001218926 pathogenic Neurofibromatosis, type 1 2019-12-20 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000578739 SCV001446559 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing

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