ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3586C>G (p.Leu1196Val)

dbSNP: rs1555615039
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000660038 SCV000781990 likely pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000660038 SCV000958325 pathogenic Neurofibromatosis, type 1 2023-02-09 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1196 of the NF1 protein (p.Leu1196Val). 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: 547629). This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 26740943; Invitae). This variant is not present in population databases (gnomAD no frequency). This variant disrupts the p.Leu1196 amino acid residue in NF1. Other variant(s) that disrupt this residue have been observed in individuals with NF1-related conditions (PMID: 15060124, 17103458, 22664660, 23047742, 27838393), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV003163040 SCV003915398 likely pathogenic not provided 2022-10-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in a cohort of individuals with clinical characteristics of neurofibromatosis type 1 (Bianchessi et al., 2015); This variant is associated with the following publications: (PMID: 25486365, 22807134, 2121369, 26740943)

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.