ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4171A>G (p.Arg1391Gly) (rs1555618515)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000548305 SCV000628574 likely pathogenic Neurofibromatosis, type 1 2017-12-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 1391 of the NF1 protein (p.Arg1391Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with neurofibromatosis type 1 (PMID: 22807134, Invitae). Experimental studies have shown that NF1 proteins containing this missense change have reduced GTPase-activating protein function, resulting in increased active levels of Ras in vitro (PMID: 22807134). A different missense substitution at this codon (p.Arg1391Ser) has been determined to be likely pathogenic (PMID: 9003501, 22807134). This suggests that the arginine residue is critical for NF1 protein function and that other missense substitutions at this position may also be pathogenic. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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.