ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.298C>G (p.Gln100Glu) (rs757841535)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000775650 SCV000910035 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-29 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781895 SCV000920286 uncertain significance not specified 2018-12-14 criteria provided, single submitter clinical testing Variant summary: STK11 c.298C>G (p.Gln100Glu) results in a conservative amino acid change located in the Protein kinase domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.1e-05 in 277144 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.298C>G in individuals affected with Peutz-Jeghers Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000632835 SCV000754031 uncertain significance Peutz-Jeghers syndrome 2018-11-16 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 100 of the STK11 protein (p.Gln100Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs757841535, ExAC 0.01%). This variant has not been reported in the literature in individuals with STK11-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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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