ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.2339C>G (p.Thr780Arg)

dbSNP: rs199474746
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000553902 SCV000628434 pathogenic Neurofibromatosis, type 1 2023-03-01 criteria provided, single submitter clinical testing This variant disrupts the p.Thr780 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10712197, 11735023, 12552569, 15146469, 16944272, 26478990; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function. ClinVar contains an entry for this variant (Variation ID: 457581). This missense change has been observed in individuals with neurofibromatosis type 1 (PMID: 16786508, 16944272, 31370276; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 780 of the NF1 protein (p.Thr780Arg).
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000553902 SCV000781949 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000553902 SCV002561755 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002448633 SCV002732368 likely pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-01-30 criteria provided, single submitter clinical testing The p.T780R variant (also known as c.2339C>G), located in coding exon 20 of the NF1 gene, results from a C to G substitution at nucleotide position 2339. The threonine at codon 780 is replaced by arginine, an amino acid with similar properties. This alteration has been identified in multiple individuals with a clinical diagnosis of neurofibromatosis type 1 (NF1) (Upadhyaya M et al. Hum. Mutat., 2006 Jul;27:716; Griffiths S et al. Fam. Cancer, 2007;6:21-34; Giugliano T et al. Genes (Basel), 2019 07;10; Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000553902 SCV002769545 likely pathogenic Neurofibromatosis, type 1 2022-12-22 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002497068 SCV002807588 likely pathogenic Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2022-04-10 criteria provided, single submitter clinical testing
GeneDx RCV000681848 SCV003806071 likely pathogenic not provided 2022-08-30 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with features of neurofibromatosis type (Upadhyaya et al., 2006; Griffiths et al., 2007; Giugliano et al., 2019; Groopman et al., 2019; Hannah-Shmouni et al., 2022); This variant is associated with the following publications: (PMID: 16944272, 25486365, 24803665, 31370276, 30586318, 35456261, 16786508)
Baylor Genetics RCV003459191 SCV004198984 likely pathogenic Juvenile myelomonocytic leukemia 2022-04-26 criteria provided, single submitter clinical testing
Gharavi Laboratory, Columbia University RCV000681848 SCV000809326 likely pathogenic not provided 2018-09-16 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.