ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.94A>G (p.Thr32Ala) (rs755210880)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229700 SCV000284882 uncertain significance Peutz-Jeghers syndrome 2018-10-10 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 32 of the STK11 protein (p.Thr32Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs755210880, ExAC 0.002%). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 237806). 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 and their clinical significance is uncertain. 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 RCV000229700 SCV000489330 uncertain significance Peutz-Jeghers syndrome 2016-09-19 criteria provided, single submitter clinical testing
GeneDx RCV000479327 SCV000565596 uncertain significance not provided 2017-09-26 criteria provided, single submitter clinical testing This variant is denoted STK11 c.94A>G at the cDNA level, p.Thr32Ala (T32A) at the protein level, and results in the change of a Threonine to an Alanine (ACC>GCC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 Thr32Ala was not observed at a significant frequency in large population cohorts (Lek 2016). Since Threonine and Alanine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. STK11 Thr32Ala occurs at a position that is not conserved and is not located in a known functional domain. 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 Thr32Ala is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000561474 SCV000664333 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000561474 SCV000686708 uncertain significance Hereditary cancer-predisposing syndrome 2016-05-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000479327 SCV000888651 uncertain significance not provided 2018-03-09 criteria provided, single submitter clinical testing
Gharavi Laboratory,Columbia University RCV000479327 SCV000920675 uncertain significance not provided 2018-09-16 no assertion criteria provided research

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.