ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1243C>G (p.Arg415Gly) (rs864622448)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206057 SCV000260679 uncertain significance Peutz-Jeghers syndrome 2018-11-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 415 of the STK11 protein (p.Arg415Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. While this variant is not present in population databases (rs864622448), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with an STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 220264). 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. In summary, this is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
GeneDx RCV000759354 SCV000566529 uncertain significance not provided 2018-07-12 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1243C>G at the cDNA level, p.Arg415Gly (R415G) at the protein level, and results in the change of an Arginine to a Glycine (CGC>GGC). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. STK11 Arg415Gly was not observed in large population cohorts (Lek 2016). This variant is located within the C-terminal region (Hearle 2006). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether STK11 Arg415Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000480161 SCV000602213 uncertain significance not specified 2016-08-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV000561859 SCV000664330 uncertain significance Hereditary cancer-predisposing syndrome 2017-02-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759354 SCV000888640 uncertain significance not provided 2018-03-27 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765435 SCV000896719 uncertain significance Carcinoma of pancreas; Peutz-Jeghers syndrome; Malignant tumor of testis 2018-10-31 criteria provided, single submitter clinical testing
Color RCV000561859 SCV000906764 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-06 criteria provided, single submitter clinical testing

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