ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1100C>T (p.Thr367Met) (rs587782835)

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 RCV000132421 SCV000187513 uncertain significance Hereditary cancer-predisposing syndrome 2017-07-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000197228 SCV000254538 uncertain significance Peutz-Jeghers syndrome 2019-01-02 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 367 of the STK11 protein (p.Thr367Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). While this variant has been published in the literature (PMID: 10676634, 15800014), it has not been reported in the germline of individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 142939). Experimental studies have shown that this missense change does not affect kinase activity of the STK11 protein (PMID: 10676634, 15800014), but partially affects the efficiency of nuclear export and AMPK activation (PMID: 15800014). 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 RCV000222146 SCV000279187 uncertain significance not provided 2017-09-21 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1100C>T at the cDNA level, p.Thr367Met (T367M) at the protein level, and results in the change of a Threonine to a Methionine (ACG>ATG). Functional studies have shown that this variant impairs the ability to regulate both cell polarity and the AMP-activated protein kinase pathway; however, another assay demonstrated that this variant does not impact protein kinase activity (Launonen 2000, Forcet 2005). STK11 Thr367Met was not observed in large population cohorts (Lek 2016, The 1000 Genomes Consortium 2015, NHLBI Exome Sequencing Project). Since Threonine and Methionine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. STK11 Thr367Met occurs at a position where amino acids with properties similar to Threonine are tolerated across species and is located within the C-terminal region (Hearle 2006). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether STK11 Thr367Met is pathogenic or benign. We consider it to be a variant of uncertain significance.
Counsyl RCV000197228 SCV000488509 uncertain significance Peutz-Jeghers syndrome 2016-04-13 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.