ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.595G>A (p.Ala199Thr)

gnomAD frequency: 0.00001  dbSNP: rs1261707371
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000553734 SCV000628878 uncertain significance Neurofibromatosis, type 2 2022-10-31 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 199 of the NF2 protein (p.Ala199Thr). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with NF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 457924). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NF2 protein function. 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 RCV001024724 SCV001186794 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-04 criteria provided, single submitter clinical testing The p.A199T variant (also known as c.595G>A), located in coding exon 6 of the NF2 gene, results from a G to A substitution at nucleotide position 595. The alanine at codon 199 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000553734 SCV002044851 uncertain significance Neurofibromatosis, type 2 2021-11-07 criteria provided, single submitter clinical testing
GeneDx RCV003236809 SCV003935787 uncertain significance not provided 2022-12-21 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 11756419, 16324214, 28852847)
CeGaT Center for Human Genetics Tuebingen RCV003236809 SCV004154850 uncertain significance not provided 2023-10-01 criteria provided, single submitter clinical testing NF2: PM2
Baylor Genetics RCV003459196 SCV004199049 uncertain significance Familial meningioma 2023-08-06 criteria provided, single submitter clinical testing

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.