ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.2458G>A (p.Val820Met)

gnomAD frequency: 0.00002  dbSNP: rs761408020
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164539 SCV000215194 uncertain significance Hereditary cancer-predisposing syndrome 2014-06-04 criteria provided, single submitter clinical testing The p.V820M variant (also known as c.2458G>A), located in coding exon 21 of the NF1 gene, results from a G to A substitution at nucleotide position 2458. The valine at codon 820 is replaced by methionine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project.<span style="background-color: initial;">To date, this alteration has been detected with an allele frequency of approximately 0.02% (greater than 5000 alleles tested) in our clinical cohort (includes this individual).<span style="background-color: initial;">This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis.<span style="background-color: initial;">Since supporting evidence is limited at this time, the clinical significance of<span style="background-color: initial;">p.V820M<span style="background-color: initial;">remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001307612 SCV001497031 uncertain significance Neurofibromatosis, type 1 2024-02-27 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 820 of the NF1 protein (p.Val820Met). This variant is present in population databases (rs761408020, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 185170). 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 NF1 protein function with a negative predictive value of 95%. 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.
Genome-Nilou Lab RCV001307612 SCV002562046 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002505206 SCV002815725 uncertain significance Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2022-02-10 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.