Total submissions: 18
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000129869 | SCV000184686 | pathogenic | Inborn genetic diseases | 2014-06-06 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000000390 | SCV000284442 | pathogenic | Neurofibromatosis, type 1 | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg1241*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with neurofibromatosis type 1 (PMID: 10712197, 12483293, 16835897, 23668869, 25624686). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 361). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000578991 | SCV000680720 | pathogenic | not provided | 2022-07-05 | 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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25049327, 28152038, 22962301, 29620724, 25525159, 12483293, 27236105, 24931142, 31730495, 31717729, 25624686, 10712197, 30530636, 17889038, 26230854, 15060124, 29089047, 16835897, 23668869) |
ARUP Laboratories, |
RCV000578991 | SCV000884244 | pathogenic | not provided | 2018-06-08 | criteria provided, single submitter | clinical testing | The NF1 c.3721C>T; p.Arg1241Ter variant (rs137854562) is reported in the literature in several individuals with NF1 (Fahsold 2000, Gupta 2015, Ko 2013, Lee 2006, Upadhyaya 2003). This variant is reported as pathogenic in ClinVar (Variation ID: 361). It is absent from the general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. 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 to be pathogenic. REFERENCES 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 Mar;66(3):790-818. Gupta V et al. Rare case of optic pathway glioma with extensive intra-ocular involvement in a child with neurofibromatosis type 1. Middle East Afr J Ophthalmol. 2015 Jan-Mar;22(1):117-8. Ko JM et al. Mutation spectrum of NF1 and clinical characteristics in 78 Korean patients with neurofibromatosis type 1. Pediatr Neurol. 2013 Jun;48(6):447-53. Lee MJ et al. Identification of forty-five novel and twenty-three known NF1 mutations in Chinese patients with neurofibromatosis type 1. Hum Mutat. 2006 Aug;27(8):832. Upadhyaya M et al. Three different pathological lesions in the NF1 gene originating de novo in a family with neurofibromatosis type 1. Hum Genet. 2003 Jan;112(1):12-7. |
Medical Genetics, |
RCV000000390 | SCV001218920 | pathogenic | Neurofibromatosis, type 1 | 2019-12-20 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics Munich, |
RCV000000390 | SCV001429942 | pathogenic | Neurofibromatosis, type 1 | 2019-05-08 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000000390 | SCV001479137 | pathogenic | Neurofibromatosis, type 1 | 2020-10-26 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000000390 | SCV001523053 | pathogenic | Neurofibromatosis, type 1 | 2019-11-14 | 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 by following sources [PMID: 10712197, 28152038, 25525159, 25624686, 17889038, 29620724, 29089047, 12483293, ClinVar ID: 361] |
Revvity Omics, |
RCV000578991 | SCV002018302 | pathogenic | not provided | 2019-03-20 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000000390 | SCV002559983 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Victorian Clinical Genetics Services, |
RCV000000390 | SCV002769466 | pathogenic | Neurofibromatosis, type 1 | 2023-07-16 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated juvenile myelomonocytic leukemia (MIM#607785), familial spinal neurofibromatosis (MIM#162210), neurofibromatosis type 1 (MIM#162200), neurofibromatosis-Noonan syndrome (MIM#601321) and Watson syndrome (MIM#193520). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Disease manifestation can be extremely variable, even within a family (GeneReviews). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other null variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Other NMD-predicted variants have been classified as likely pathogenic or pathogenic (DECIPHER). (SP) 0801 - This variant has very strong previous evidence of pathogenicity in unrelated individuals. This variant has been classified as pathogenic by multiple clinical diagnostic laboratories and has been reported in multiple unrelated individuals with neurofibromatosis type 1 (ClinVar; PMIDs: 16835897, 33919865). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
Baylor Genetics | RCV003466769 | SCV004190717 | pathogenic | Juvenile myelomonocytic leukemia | 2023-05-24 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000578991 | SCV004227861 | pathogenic | not provided | 2022-04-28 | criteria provided, single submitter | clinical testing | PP4, PM2, PM6, PS4_moderate, PVS1 |
OMIM | RCV000000390 | SCV000020534 | pathogenic | Neurofibromatosis, type 1 | 2003-01-01 | no assertion criteria provided | literature only | |
Clinical Molecular Genetics Laboratory, |
RCV000000390 | SCV000692349 | pathogenic | Neurofibromatosis, type 1 | 2015-01-21 | no assertion criteria provided | clinical testing | |
Diagnostic Laboratory, |
RCV000578991 | SCV001742680 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000578991 | SCV001964169 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Division of Human Genetics, |
RCV000000390 | SCV003840164 | pathogenic | Neurofibromatosis, type 1 | no assertion criteria provided | research |