ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.5230A>G (p.Thr1744Ala) (rs747584987)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000572932 SCV000663150 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Center for Human Genetics, Inc RCV000466099 SCV000782047 uncertain significance Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
GeneDx RCV000679398 SCV000808685 uncertain significance not provided 2018-04-26 criteria provided, single submitter clinical testing This variant is denoted NF1 c.5230A>G at the cDNA level, p.Thr1744Ala (T1744A) at the protein level, and results in the change of a Threonine to an Alanine (ACT>GCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NF1 Thr1744Ala was observed at an allele frequency of 0.006% (2/33576) in individuals of Latino ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether NF1 Thr1744Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000466099 SCV000542054 uncertain significance Neurofibromatosis, type 1 2018-10-05 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 1744 of the NF1 protein (p.Thr1744Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs747584987, ExAC 0.009%). This variant has not been reported in the literature in individuals with NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 404477). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
PreventionGenetics RCV000679398 SCV000806294 uncertain significance not provided 2017-11-22 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.