ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.304A>G (p.Met102Val) (rs756370324)

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 RCV000565942 SCV000670345 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
GeneDx RCV000681271 SCV000808733 uncertain significance not provided 2018-05-01 criteria provided, single submitter clinical testing This variant is denoted NF1 c.304A>G at the cDNA level, p.Met102Val (M102V) at the protein level, and results in the change of a Methionine to a Valine (ATG>GTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NF1 Met102Val was observed at an allele frequency of 0.002% (2/111420) in individuals of European ancestry 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 Met102Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000532623 SCV000628484 uncertain significance Neurofibromatosis, type 1 2018-08-03 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 102 of the NF1 protein (p.Met102Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs756370324, ExAC 0.002%). This variant has not been reported in the literature in individuals with NF1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.