ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.614C>T (p.Ala205Val) (rs587782468)

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 RCV000131568 SCV000186572 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000168319 SCV000219004 uncertain significance Peutz-Jeghers syndrome 2018-10-31 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 205 of the STK11 protein (p.Ala205Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs587782468, ExAC 0.01%). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 142443). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Counsyl RCV000168319 SCV000487863 uncertain significance Peutz-Jeghers syndrome 2015-11-23 criteria provided, single submitter clinical testing
GeneDx RCV000486177 SCV000566571 uncertain significance not provided 2018-07-09 criteria provided, single submitter clinical testing This variant is denoted STK11 c.614C>T at the cDNA level, p.Ala205Val (A205V) at the protein level, and results in the change of an Alanine to a Valine (GCG>GTG). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. STK11 Ala205Val was not observed in large population cohorts (Lek 2016). This variant is located in the protein kinase domain and the region of binding of substrate and initiation of phospho transfer (Hearle 2006, UniProt). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether STK11 Ala205Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000131568 SCV000686670 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-23 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.