Total submissions: 18
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000457194 | SCV000542202 | pathogenic | Neurofibromatosis, type 1 | 2024-01-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg1306*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with neurofibromatosis type 1 (PMID: 9783703, 10712197, 15146469, 16835897, 16944272, 26969325). ClinVar contains an entry for this variant (Variation ID: 404592). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000489457 | SCV000577115 | pathogenic | not provided | 2024-01-08 | 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 (PMID: 9783703); This variant is associated with the following publications: (PMID: 31066482, 28955729, 34418705, 31533797, 29922827, 32164600, 25525159, 16835897, 16944272, 10712197, 15146469, 12112660, 11735023, 12552569, 22155606, 26969325, 30530636, 29957862, 9783703, 31347283, 31370276, 30877234, 29625052, 31776437, Krat[case reeport], 33593231, 34694046, 33877690, 35418823, 27535533, 30308447) |
Center for Human Genetics, |
RCV000457194 | SCV000782006 | pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Blueprint Genetics | RCV000489457 | SCV000927881 | pathogenic | not provided | 2018-08-24 | criteria provided, single submitter | clinical testing | |
Clinical Molecular Genetics Laboratory, |
RCV000457194 | SCV001156511 | pathogenic | Neurofibromatosis, type 1 | 2020-02-03 | criteria provided, single submitter | clinical testing | |
The Laboratory of Genetics and Metabolism, |
RCV001009594 | SCV001169695 | pathogenic | Neurofibromatosis, type 1; Tibial pseudarthrosis | 2018-11-10 | criteria provided, single submitter | research | |
Ambry Genetics | RCV002318998 | SCV001183047 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2019-02-23 | criteria provided, single submitter | clinical testing | The p.R1306* pathogenic mutation (also known as c.3916C>T), located in coding exon 29 of the NF1 gene, results from a C to T substitution at nucleotide position 3916. This changes the amino acid from an arginine to a stop codon within coding exon 29. This mutation has been detected in several individuals, once as a de novo occurrence, meeting NIH diagnostic criteria for Neurofibromatosis type 1 (NF1) (Marwaha A et al. Br. J. Dermatol., 2018 Nov;179:1216-1217, Tsipi M et al. J. Neurol. Sci., 2018 Dec;395:95-105).Park VM et al. J. Med. Genet., 1998 Oct;35:813-20; Fahsold R et al. Am. J. Hum. Genet., 2000 Mar;66:790-818; Lee MJ et al. Hum Mutat. 2006 Aug;27(8):832; Hutter S et al. Hum Genet. 2016 May;135(5):469-75). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000457194 | SCV001431876 | pathogenic | Neurofibromatosis, type 1 | 2020-08-31 | criteria provided, single submitter | clinical testing | Variant summary: NF1 c.3916C>T (p.Arg1306X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251422 control chromosomes. c.3916C>T has been reported in the literature in multiple individuals affected with Neurofibromatosis Type 1 (Fahsold_2000, Sabbagh_2013). These data indicate that the variant is very likely to be associated with disease. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (pathongenic n=6, VUS n=1). Based on the evidence outlined above, the variant was classified as pathogenic. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000489457 | SCV001470147 | pathogenic | not provided | 2020-05-14 | criteria provided, single submitter | clinical testing | The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity. |
Athena Diagnostics | RCV000489457 | SCV001476707 | pathogenic | not provided | 2020-05-14 | criteria provided, single submitter | clinical testing | The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity. |
Genome Diagnostics Laboratory, |
RCV000457194 | SCV001479008 | pathogenic | Neurofibromatosis, type 1 | 2020-10-26 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000489457 | SCV001746524 | pathogenic | not provided | 2022-10-01 | criteria provided, single submitter | clinical testing | NF1: PVS1, PM2, PS4:Moderate |
Genome- |
RCV000457194 | SCV002560006 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000457194 | SCV004041021 | pathogenic | Neurofibromatosis, type 1 | 2023-05-02 | criteria provided, single submitter | clinical testing | |
Clinical Genomics Laboratory, |
RCV000457194 | SCV004176958 | pathogenic | Neurofibromatosis, type 1 | 2023-08-27 | criteria provided, single submitter | clinical testing | The NF1 c.3916C>T (p.Arg1306Ter) variant was identified at near heterozygous allelic fraction. This variant leads to a premature termination codon, which is predicted to lead to nonsense mediated decay. It has been reported in several individuals affected with neurofibromatosis type 1 (Sabbagh A et al., PMID: 23913538; Chen L et al., PMID: 31347283; Wiest V et al., PMID: 14635100; Thomas L et al., PMID: 22108604; Zhu G et al., PMID: 31533797). This variant has been reported as a somatic variant in 13 cases in the cancer database COSMIC and has been reported in the ClinVar database as pathogenic by 12 submitters (ClinVar ID: 404592). The NF1 c.3916C>T (p.Arg1306Ter) variant is absent from the general population (gnomAD v.3.1.2), indicating it is not a common variant. Based on available information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the NF1 c.3916C>T (p.Arg1306Ter) variant is classified as pathogenic and clinically significant. |
Baylor Genetics | RCV003470401 | SCV004190748 | pathogenic | Juvenile myelomonocytic leukemia | 2023-04-14 | criteria provided, single submitter | clinical testing | |
NHS Central & South Genomic Laboratory Hub | RCV000457194 | SCV005395910 | pathogenic | Neurofibromatosis, type 1 | 2024-11-12 | criteria provided, single submitter | clinical testing | |
Biochemical Molecular Genetic Laboratory, |
RCV000457194 | SCV001190825 | uncertain significance | Neurofibromatosis, type 1 | 2020-02-05 | no assertion criteria provided | clinical testing |