ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.248A>G (p.Lys83Arg) (rs374006397)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000217408 SCV000279527 uncertain significance not provided 2017-06-09 criteria provided, single submitter clinical testing This variant is denoted STK11 c.248A>G at the cDNA level, p.Lys83Arg (K83R) at the protein level, and results in the change of a Lysine to an Arginine (AAG>AGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 Lys83Arg was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Lysine and Arginine share similar properties, this is considered a conservative amino acid substitution. STK11 Lys83Arg occurs at a position that is not conserved and is located in the protein kinase domain, a region sufficient for interaction with SIRT1, and the domain responsible for binding and orientation of ATP (Hearle 2006, 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 Lys83Arg is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000539793 SCV000629100 uncertain significance Peutz-Jeghers syndrome 2018-04-17 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 83 of the STK11 protein (p.Lys83Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs374006397, ExAC 0.01%). This variant has not been reported in the literature in individuals with a STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 234584). 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, this variant has uncertain impact on STK11 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000565378 SCV000675256 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000565378 SCV000686625 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-16 criteria provided, single submitter clinical testing

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