ClinVar Miner

Submissions for variant NM_000455.5(STK11):c.334C>G (p.Gln112Glu)

gnomAD frequency: 0.00001  dbSNP: rs771049807
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165050 SCV000215750 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-02 criteria provided, single submitter clinical testing The p.Q112E variant (also known as c.334C>G), located in coding exon 2 of the STK11 gene, results from a C to G substitution at nucleotide position 334. The glutamine at codon 112 is replaced by glutamic acid, an amino acid with highly similar properties. Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000457693 SCV000541117 uncertain significance Peutz-Jeghers syndrome 2023-08-05 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with STK11-related conditions. This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 112 of the STK11 protein (p.Gln112Glu). This variant is present in population databases (rs771049807, gnomAD 0.002%). ClinVar contains an entry for this variant (Variation ID: 185602). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt STK11 protein function. Experimental studies have shown that this missense change does not substantially affect STK11 function (PMID: 34849607). 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.
Color Diagnostics, LLC DBA Color Health RCV000165050 SCV001343313 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-25 criteria provided, single submitter clinical testing This missense variant replaces glutamine with glutamic acid at codon 112 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Functional studies have shown that the mutant protein retained autophosphorylation activity in an in vitro kinase assay (PMID: 34849607). This variant has been reported in an individual affected with advanced cancer (PMID: 28873162). This variant has been identified in 2/249176 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Genome-Nilou Lab RCV000457693 SCV002057772 uncertain significance Peutz-Jeghers syndrome 2021-07-15 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000165050 SCV002531683 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-05 criteria provided, single submitter curation
All of Us Research Program, National Institutes of Health RCV000457693 SCV004816344 uncertain significance Peutz-Jeghers syndrome 2023-09-18 criteria provided, single submitter clinical testing This missense variant replaces glutamine with glutamic acid at codon 112 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Functional studies have shown that the mutant protein retained autophosphorylation activity in an in vitro kinase assay (PMID: 34849607). This variant has been reported in an individual affected with advanced cancer (PMID: 28873162). This variant has been identified in 2/249176 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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