ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4098C>G (p.His1366Gln)

gnomAD frequency: 0.00001  dbSNP: rs1555617377
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000632493 SCV000753678 likely benign Neurofibromatosis, type 1 2024-08-27 criteria provided, single submitter clinical testing
GeneDx RCV000681301 SCV000808763 uncertain significance not provided 2018-05-18 criteria provided, single submitter clinical testing This variant is denoted NF1 c.4098C>G at the cDNA level, p.His1366Gln (H1366Q) at the protein level, and results in the change of a Histidine to a Glutamine (CAC>CAG). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. NF1 His1366Gln was not observed in large population cohorts (Lek 2016). This variant is located in the GTPase activating protein domain (Thomas 2012, Luo 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether NF1 His1366Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV002319063 SCV001183520 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-03-09 criteria provided, single submitter clinical testing The p.H1366Q variant (also known as c.4098C>G), located in coding exon 30 of the NF1 gene, results from a C to G substitution at nucleotide position 4098. The histidine at codon 1366 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000632493 SCV002560379 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Baylor Genetics RCV004568381 SCV005052208 uncertain significance Juvenile myelomonocytic leukemia 2024-03-03 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005019050 SCV005646746 uncertain significance Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2024-04-22 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004547784 SCV004712756 uncertain significance NF1-related disorder 2023-11-21 no assertion criteria provided clinical testing The NF1 c.4098C>G variant is predicted to result in the amino acid substitution p.His1366Gln. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/527583/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.