ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.970C>G (p.Pro324Ala) (rs549474196)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000213028 SCV000149515 likely benign not specified 2017-10-27 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000115606 SCV000183870 likely benign Hereditary cancer-predisposing syndrome 2018-09-04 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other strong data supporting benign classification
Invitae RCV000168083 SCV000218737 benign Peutz-Jeghers syndrome 2020-12-01 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000168083 SCV000257695 uncertain significance Peutz-Jeghers syndrome 2015-07-21 criteria provided, single submitter clinical testing
Counsyl RCV000168083 SCV000487903 uncertain significance Peutz-Jeghers syndrome 2015-12-04 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001281717 SCV000602247 likely benign not provided 2020-01-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000213028 SCV000696735 likely benign not specified 2018-08-17 criteria provided, single submitter clinical testing Variant summary: STK11 c.970C>G (p.Pro324Ala) results in a non-conservative amino acid change located in the Serine/Threonine kinase LKB1, catalytic domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.5e-05 in 244678 control chromosomes (gnomAD). The observed variant frequency is approximately 7-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in STK11 causing Peutz-Jeghers Syndrome phenotype (6.3e-06), strongly suggesting that the variant is benign. c.970C>G has been reported in the literature in an individual affected with Lynch syndrome (Yurgelun_2015) and undergoing hereditary cancer risk assessment (Selkirk_2014). These report(s) do not provide unequivocal conclusions about association of the variant with Peutz-Jeghers Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cite the variant as "uncertain significance" (3x) and "likely benign" (3x). Based on the evidence outlined above, the variant was classified as likely benign.
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital RCV000761091 SCV000891006 uncertain significance Acute monocytic leukemia; Acute monoblastic leukemia 2016-07-20 criteria provided, single submitter clinical testing
Color Health, Inc RCV000115606 SCV000902726 likely benign Hereditary cancer-predisposing syndrome 2016-03-23 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000213028 SCV000692054 uncertain significance not specified no assertion criteria provided clinical testing

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