ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1016C>T (p.Pro339Leu) (rs567896256)

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 RCV000132059 SCV000187121 uncertain significance Hereditary cancer-predisposing syndrome 2016-12-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000226438 SCV000284838 uncertain significance Peutz-Jeghers syndrome 2018-10-01 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 339 of the STK11 protein (p.Pro339Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 142696). 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 C15"). 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.
GeneDx RCV000483861 SCV000567655 uncertain significance not provided 2018-04-11 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1016C>T at the cDNA level, p.Pro339Leu (P339L) at the protein level, and results in the change of a Proline to a Leucine (CCG>CTG). This variant has not, to our knowledge, been published in the literature as a germline variant; however, it has been reported as a somatic variant in a colon tumor (Goswami 2015). STK11 Pro339Leu was not observed at a significant allele frequency 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 STK11 Pro339Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000132059 SCV000686574 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-30 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.