ClinVar Miner

Submissions for variant NM_000455.5(STK11):c.1120G>A (p.Glu374Lys)

gnomAD frequency: 0.00001  dbSNP: rs587782287
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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 RCV000492193 SCV000580945 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-21 criteria provided, single submitter clinical testing The p.E374K variant (also known as c.1120G>A), located in coding exon 9 of the STK11 gene, results from a G to A substitution at nucleotide position 1120. The glutamic acid at codon 374 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.
Invitae RCV000531354 SCV000629062 uncertain significance Peutz-Jeghers syndrome 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 374 of the STK11 protein (p.Glu374Lys). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 428789). 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 with a negative predictive value of 95%. 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.
Genome-Nilou Lab RCV000531354 SCV002057932 uncertain significance Peutz-Jeghers syndrome 2021-07-15 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000531354 SCV004826062 uncertain significance Peutz-Jeghers syndrome 2023-05-15 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 374 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with STK11-related disorders in the literature. This variant has been identified in 1/241280 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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