ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.662A>G (p.Tyr221Cys) (rs746025177)

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
Invitae RCV000694486 SCV000822934 uncertain significance Neurofibromatosis, type 2 2019-10-20 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 221 of the NF2 protein (p.Tyr221Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs746025177, ExAC 0.03%). This variant has not been reported in the literature in individuals with NF2-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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Ambry Genetics RCV001025472 SCV001187668 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-17 criteria provided, single submitter clinical testing The p.Y221C variant (also known as c.662A>G), located in coding exon 7 of the NF2 gene, results from an A to G substitution at nucleotide position 662. The tyrosine at codon 221 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.