ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.310A>G (p.Arg104Gly) (rs587782783)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160999 SCV000211709 uncertain significance not provided 2017-03-07 criteria provided, single submitter clinical testing This variant is denoted STK11 c.310A>G at the cDNA level, p.Arg104Gly (R104G) at the protein level, and results in the change of an Arginine to a Glycine (AGG>GGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 Arg104Gly was not observed at a significan allele frequency in in the Exome Aggregation Consortium (ExAC) database (Lek 2016). Since Arginine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. STK11 Arg104Gly occurs at a position that is conserved across species and is located in the protein kinase domain as well as the domain of binding and orientation of ATP (Hearle 2006, UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether STK11 Arg104Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000233314 SCV000284860 uncertain significance Peutz-Jeghers syndrome 2018-05-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 104 of the STK11 protein (p.Arg104Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is present in population databases (rs587782783, ExAC 0.002%). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 182905). 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 disruptive, 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.
Counsyl RCV000233314 SCV000489355 uncertain significance Peutz-Jeghers syndrome 2016-09-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV000569641 SCV000664340 uncertain significance Hereditary cancer-predisposing syndrome 2016-12-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or Conflicting Evidence

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