ClinVar Miner

Submissions for variant NM_000455.5(STK11):c.542A>G (p.Asn181Ser) (rs886037859)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Shenzhen Institute of Pediatrics,Shenzhen Children's Hospital RCV000241351 SCV000298003 likely pathogenic Peutz-Jeghers syndrome 2016-08-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000492112 SCV000580896 pathogenic Hereditary cancer-predisposing syndrome 2020-09-23 criteria provided, single submitter clinical testing The p.N181S pathogenic mutation (also known as c.542A>G), located in coding exon 4 of the STK11 gene, results from an A to G substitution at nucleotide position 542. The asparagine at codon 181 is replaced by serine, an amino acid with highly similar properties. This alteration was identified in two first-degree relatives from a family suspected of having Peutz-Jeghers syndrome (Ambry internal data). Based on an internal structural assessment, this alteration disrupts the Mg-ATP binding in the active site of STK11 (Zeqiraj E et al. Science, 2009 Dec;326:1707-11; Gerlits O et al. Biochemistry, 2013 May;52:3721-7). Other alterations at the same codon (p.N181K, p.N181Y, p.N181T, p.N181E) have also been identified in individuals either diagnosed with or suspected to have Peutz-Jeghers syndrome (Ambry internal data; Ylikorkala A et al. Hum. Mol. Genet., 1999 Jan;8:45-51; Connolly DC et al. Am. J. Pathol., 2000 Jan;156:339-45; Amos CI et al. J. Med. Genet., 2004 May;41:327-33). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Invitae RCV000241351 SCV000754014 pathogenic Peutz-Jeghers syndrome 2018-03-09 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 181 of the STK11 protein (p.Asn181Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual with features consistent with Peutz-Jeghers syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 254654). 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 and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Color Health, Inc RCV000492112 SCV000905234 likely pathogenic Hereditary cancer-predisposing syndrome 2020-02-06 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.