ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1088C>T (p.Thr363Ile) (rs587778695)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219976 SCV000277985 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000219976 SCV000691466 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-30 criteria provided, single submitter clinical testing
Counsyl RCV000206210 SCV000489312 uncertain significance Peutz-Jeghers syndrome 2016-09-16 criteria provided, single submitter clinical testing
Database of Curated Mutations (DoCM) RCV000206210 SCV000510522 likely pathogenic Peutz-Jeghers syndrome 2016-05-13 no assertion criteria provided literature only
GeneDx RCV000656983 SCV000565599 uncertain significance not provided 2017-06-23 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1088C>T at the cDNA level, p.Thr363Ile (T363I) at the protein level, and results in the change of a Threonine to an Isoleucine (ACT>ATT). This variant was observed in two Chinese brothers affected with Peutz-Jehgers syndrome (Liu 2012) and an individual with breast cancer (Tung 2015) as well as healthy controls (Wei 2011, Bodian 2014). STK11 Thr363Ile was observed at an allele frequency of 0.12% (9/7562) in individuals of East Asian ancestry in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Threonine and Isoleucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. STK11 Thr363Ile occurs at a position that is conserved across species and is not located in a known functional domain, although Thr363 is an autophosphorylation site (Baas 2003, Hearle 2006). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether STK11 Thr363Ile is pathogenic or benign. We consider it to be a variant of uncertain significance.
ITMI RCV000122092 SCV000086307 not provided not specified 2013-09-19 no assertion provided reference population
Invitae RCV000206210 SCV000259712 likely benign Peutz-Jeghers syndrome 2017-04-07 criteria provided, single submitter clinical testing

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