ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.910C>T (p.Arg304Ter) (rs786203950)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167474 SCV000218330 pathogenic Hereditary cancer-predisposing syndrome 2014-12-26 criteria provided, single submitter clinical testing The p.R304* pathogenic mutation (also known as c.910C>T), located in coding exon 9 of the NF1 gene, results from a C to T substitution at nucleotide position 910. This changes the amino acid from an arginine to a stop codon within coding exon 9. This mutation has been observed in multiple individuals meeting clinical diagnostic criteria for NF1 (De Luca, A et al. Hum Mutat. 2004 Jun;23(6):629; Fahsold, R et al. Am J Hum Genet. 2000 Mar;66(3):790-818; Upadhyaya, M et al. Hum Mutat. 2008 Aug;29(8):E103-11; Ko, JM et al. Pediatr Neurol. 2013 Jun;48(6):447-53). 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 RCV000468520 SCV000542003 pathogenic Neurofibromatosis, type 1 2020-10-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 304 (p.Arg304*) of the NF1 gene. This variant is not present in population databases (rs786203950, ExAC no frequency). This variant has been reported in the literature in individuals affected with neurofibromatosis, type 1 (PMID: 23668869, 16786508, 23913538, 10862084). ClinVar contains an entry for this variant (Variation ID: 187722). Experimental studies have shown that instead of creating a truncated protein, this variant causes skipping of exon 9 (also known as exon 7 in the literature). This creates a smaller transcript which lacks these codons and is expressed at a decreased amount when compared to wild-type transcript (PMID: 9463322, 10874316). For these reasons, this variant has been classified as Pathogenic.
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000468520 SCV000590893 pathogenic Neurofibromatosis, type 1 2017-06-06 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000508304 SCV000604459 pathogenic not specified 2018-08-15 criteria provided, single submitter clinical testing The NF1 c.910C>T; p.Arg304Ter variant (rs786203950) has been described in several individuals with neurofibromatosis type 1 (NF1) (see link below, Ko 2013, Upadhyaya 2008). It is reported as pathogenic in ClinVar (Variation ID: 187722) and observed on only 1 allele in the Genome Aggregation Database. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered pathogenic. References: Link to NF1 LOVD Database for p.Arg304Ter: Ko JM et al. (2013) Mutation spectrum of NF1 and clinical characteristics in 78 Korean patients with neurofibromatosis type 1. Pediatr Neurol. 48(6):447-53. Upadhyaya M et al. (2008) Germline and somatic NF1 gene mutations in plexiform neurofibromas. Hum Mutat. 29(8):E103-11.
GeneDx RCV000579282 SCV000680718 pathogenic not provided 2021-05-10 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 9463322, 12112660, 10874316, 10862084, 30290804, 30014477, 23913538, 29695767, 27838393, 29680440, 28247034, 10712197, 23781326, 18484666, 23668869, 12057013, 12095621, 26509978, 17295913, 25525159, 16786508)
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000468520 SCV000781883 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Medical Genetics, University of Parma RCV000468520 SCV001218910 pathogenic Neurofibromatosis, type 1 2019-12-20 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000468520 SCV001368730 pathogenic Neurofibromatosis, type 1 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS3.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000579282 SCV001446786 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV000468520 SCV001479110 pathogenic Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Baylor Genetics RCV001294062 SCV001482855 pathogenic Juvenile myelomonocytic leukemia 2020-02-12 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing [PMID 9463322, 26509978, 10874316, 25525159]
Coyote Medical Laboratory (Beijing),Coyote RCV000468520 SCV001441284 pathogenic Neurofibromatosis, type 1 2017-10-29 no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000579282 SCV001959590 pathogenic not provided no assertion criteria provided clinical testing

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