ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1A>G (p.Met1Val)

dbSNP: rs1060500252
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476863 SCV000541981 pathogenic Neurofibromatosis, type 1 2023-12-16 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the NF1 mRNA. The next in-frame methionine is located at codon 68. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individuals with neurofibromatosis type 1 (PMID: 23668869, 23913538). ClinVar contains an entry for this variant (Variation ID: 404429). For these reasons, this variant has been classified as Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV000476863 SCV001479044 pathogenic Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University RCV000476863 SCV001571441 pathogenic Neurofibromatosis, type 1 2021-02-03 criteria provided, single submitter clinical testing
Pars Genome Lab RCV000476863 SCV001653524 pathogenic Neurofibromatosis, type 1 2021-06-01 criteria provided, single submitter clinical testing This variant has been found in a 4-year-old girl with multiple Cafe-au-lait spots.
GeneDx RCV001556803 SCV001778446 pathogenic not provided 2022-10-28 criteria provided, single submitter clinical testing Initiation codon variant in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30308447, 23668869, 18041031, 23913538, 31776437, 20844836)
Genome-Nilou Lab RCV000476863 SCV002561534 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002418350 SCV002724204 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-09-28 criteria provided, single submitter clinical testing The p.M1? pathogenic mutation (also known as c.1A>G) is located in coding exon 1 of the NF1 gene and results from a A to G substitution at nucleotide position 1. This alters the methionine residue at the initiation codon (ATG). This alteration has been reported in several individuals with a clinical diagnosis of neurofibromatosis type 1 (NF1) (Brinckmann A et al. Electrophoresis, 2007 Dec;28:4295-301; Ko JM et al. Pediatr. Neurol., 2013 Jun;48:447-53; Sabbagh A et al. Hum. Mutat., 2013 Nov;34:1510-8; Tsipi M et al. J Neurol Sci. 2018 Dec 15;395:95-105; Kang E et al. J Hum Genet. 2020 Jan;65(2):79-89). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001556803 SCV002037371 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001556803 SCV002038347 pathogenic not provided no assertion criteria provided clinical testing

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