ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.301C>G (p.Leu101Val) (rs587780716)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000568071 SCV000672349 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient evidence
GeneDx RCV000588542 SCV000211708 uncertain significance not provided 2018-01-03 criteria provided, single submitter clinical testing This variant is denoted STK11 c.301C>G at the cDNA level, p.Leu101Val (L101V) at the protein level, and results in the change of a Leucine to a Valine (CTA>GTA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 Leu101Val was not observed in large population cohorts (Lek 2016). STK11 Leu101Val is located in the protein kinase domain and the domain of binding and orientation of ATP (UniProt, Hearle 2006). In-silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether STK11 Leu101Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000588542 SCV000696715 uncertain significance not provided 2015-10-30 criteria provided, single submitter clinical testing
Invitae RCV000123058 SCV000166353 uncertain significance Peutz-Jeghers syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 101 of the STK11 protein (p.Leu101Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. 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: 135919). 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: "Probably Damaging"; Align-GVGD: "Class C15"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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