ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.374G>A (p.Arg125His) (rs149003051)

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
Ambry Genetics RCV000573497 SCV000663068 uncertain significance Hereditary cancer-predisposing syndrome 2015-12-30 criteria provided, single submitter clinical testing
GeneDx RCV000681097 SCV000808553 uncertain significance not provided 2018-02-01 criteria provided, single submitter clinical testing This variant is denoted NF1 c.374G>A at the cDNA level, p.Arg125His (R125H) at the protein level, and results in the change of an Arginine to a Histidine (CGT>CAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NF1 Arg125His was not observed in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether NF1 Arg125His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000685560 SCV000813045 uncertain significance Neurofibromatosis, type 1 2018-11-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 125 of the NF1 protein (p.Arg125His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs149003051, ExAC 0.001%). This variant has not been reported in the literature in individuals with NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 480081). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.