ClinVar Miner

Submissions for variant NM_005359.6(SMAD4):c.686T>G (p.Leu229Arg)

dbSNP: rs75667697
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
Invitae RCV002233865 SCV000933992 uncertain significance Juvenile polyposis syndrome 2023-12-01 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 229 of the SMAD4 protein (p.Leu229Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with pancreatic cancer (PMID: 24465802). ClinVar contains an entry for this variant (Variation ID: 641352). 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 SMAD4 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.
Sema4, Sema4 RCV002257956 SCV002538342 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-06 criteria provided, single submitter curation
Ambry Genetics RCV002360919 SCV002665623 uncertain significance Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome 2019-05-13 criteria provided, single submitter clinical testing The p.L229R variant (also known as c.686T>G), located in coding exon 5 of the SMAD4 gene, results from a T to G substitution at nucleotide position 686. The leucine at codon 229 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.