ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.317G>A (p.Arg106Gln) (rs375622587)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479549 SCV000569735 uncertain significance not provided 2016-03-28 criteria provided, single submitter clinical testing This variant is denoted STK11 c.317G>A at the cDNA level, p.Arg106Gln (R106Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGG>CAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 Arg106Gln was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. STK11 Arg106Gln occurs at a position that is conserved in mammals and is located in the protein kinase domain (Uniprot). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether STK11 Arg106Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000573267 SCV000675263 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000573267 SCV000686631 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-14 criteria provided, single submitter clinical testing
Invitae RCV000796866 SCV000936398 uncertain significance Peutz-Jeghers syndrome 2018-09-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 106 of the STK11 protein (p.Arg106Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs375622587, 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: 420770). 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.

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