ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.2248A>G (p.Thr750Ala) (rs748064845)

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 RCV000165422 SCV000216151 uncertain significance Hereditary cancer-predisposing syndrome 2015-05-21 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 RCV000681212 SCV000808672 uncertain significance not provided 2018-04-20 criteria provided, single submitter clinical testing This variant is denoted NF1 c.2248A>G at the cDNA level, p.Thr750Ala (T750A) at the protein level, and results in the change of a Threonine to an Alanine (ACA>GCA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NF1 Thr750Ala was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the GTPase activating protein domain (Luo 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether NF1 Thr750Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance
Invitae RCV000465924 SCV000541994 uncertain significance Neurofibromatosis, type 1 2018-12-08 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 750 of the NF1 protein (p.Thr750Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs748064845, ExAC 0.002%) but has not been reported in the literature in individuals with an NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 185917). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV000465924 SCV000839137 uncertain significance Neurofibromatosis, type 1 2018-07-02 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.