ClinVar Miner

Submissions for variant NM_005359.5(SMAD4):c.175A>G (p.Thr59Ala) (rs587781977)

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 RCV000130371 SCV000185225 uncertain significance Hereditary cancer-predisposing syndrome 2013-12-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient or conflicting evidence
Counsyl RCV000411833 SCV000489156 uncertain significance Juvenile polyposis syndrome 2016-08-31 criteria provided, single submitter clinical testing
Invitae RCV000411833 SCV000632775 uncertain significance Juvenile polyposis syndrome 2017-03-08 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 59 of the SMAD4 protein (p.Thr59Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SMAD4-related disease. ClinVar contains an entry for this variant (Variation ID: 141740). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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.

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.