ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1127G>A (p.Arg376Gln) (rs996964764)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000564289 SCV000674148 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-14 criteria provided, single submitter clinical testing The p.R376Q variant (also known as c.1127G>A), located in coding exon 12 of the NF2 gene, results from a G to A substitution at nucleotide position 1127. The arginine at codon 376 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000792747 SCV000932063 uncertain significance Neurofibromatosis, type 2 2019-11-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 376 of the NF2 protein (p.Arg376Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF2-related disease. ClinVar contains an entry for this variant (Variation ID: 485984). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.