ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.827G>T (p.Gly276Val) (rs749927908)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459041 SCV000541163 uncertain significance Peutz-Jeghers syndrome 2018-09-19 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 276 of the STK11 protein (p.Gly276Val). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs749927908, 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: 403794). 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.
GeneDx RCV000487182 SCV000567908 uncertain significance not provided 2018-12-27 criteria provided, single submitter clinical testing This variant is denoted STK11 c.827G>T at the cDNA level, p.Gly276Val (G276V) at the protein level, and results in the change of a Glycine to a Valine (GGC>GTC). This variant been reported in an individual with colorectal cancer who also carried a pathogenic variant in MLH1 (Ricker 2017). STK11 Gly276Val was not observed at a significant frequency in large population cohorts (Lek 2016). This variant is located in the protein kinase domain (Schumacher 2005). 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 Gly276Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000572801 SCV000664361 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Color RCV000572801 SCV000910048 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-14 criteria provided, single submitter clinical testing

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