ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.613G>A (p.Ala205Thr) (rs730881981)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000161003 SCV000213625 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000161003 SCV000905826 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-06 criteria provided, single submitter clinical testing
Counsyl RCV000200492 SCV000784910 uncertain significance Peutz-Jeghers syndrome 2017-02-03 criteria provided, single submitter clinical testing
GeneDx RCV000200996 SCV000211713 uncertain significance not specified 2016-11-08 criteria provided, single submitter clinical testing This variant is denoted STK11 c.613G>A at the cDNA level, p.Ala205Thr (A205T) at the protein level, and results in the change of an Alanine to a Threonine (GCG>ACG). This variant was observed in at least one woman with triple negative breast cancer (Couch 2015). In a functional study on a head/neck squamous cell carcinoma cell line, this variant impaired the ability of STK11 to suppress cell growth and to decrease kinase activity (Qui 2006). STK11 Ala205Thr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Alanine and Threonine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. STK11 Ala205Thr occurs at a position that is conserved across species and is located in the protein kinase domain (Hearle 2006). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether STK11 Ala205Thr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000161003 SCV000679744 uncertain significance Hereditary cancer-predisposing syndrome 2017-07-12 criteria provided, single submitter clinical testing
Invitae RCV000200492 SCV000254554 uncertain significance Peutz-Jeghers syndrome 2018-08-18 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 205 of the STK11 protein (p.Ala205Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs730881981, ExAC 0.01%). This variant has been reported in an individual affected with triple negative breast cancer (PMID: 25452441). ClinVar contains an entry for this variant (Variation ID: 182909). Experimental studies are conflicting with regards to the effect of this missense change on STK11 activity in vitro (PMID: 16407837, 19892943). 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.
Mendelics RCV000200492 SCV000839416 uncertain significance Peutz-Jeghers syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000760084 SCV000889864 uncertain significance not provided 2018-01-28 criteria provided, single submitter clinical testing

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