ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.7762G>A (p.Val2588Ile) (rs786203848)

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 RCV000167335 SCV000218186 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes)
GeneDx RCV000681023 SCV000808473 uncertain significance not provided 2017-03-13 criteria provided, single submitter clinical testing This variant is denoted NF1 c.7762G>A at the cDNA level, p.Val2588Ile (V2588I) at the protein level, and results in the change of a Valine to an Isoleucine (GTA>ATA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NF1 Val2588Ile was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Valine and Isoleucine share similar properties, this is considered a conservative amino acid substitution. NF1 Val2588Ile occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether NF1 Val2588Ile is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000693562 SCV000821435 uncertain significance Neurofibromatosis, type 1 2018-10-15 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 2588 of the NF1 protein (p.Val2588Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 187592). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.