ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1027G>A (p.Asp343Asn) (rs368547224)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129286 SCV000184047 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000129286 SCV000537536 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-23 criteria provided, single submitter clinical testing
GeneDx RCV000656982 SCV000211723 uncertain significance not provided 2018-10-16 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1027G>A at the cDNA level, p.Asp343Asn (D343N) at the protein level, and results in the change of an Aspartic Acid to an Asparagine (GAC>AAC). This variant has been reported in a pediatric patient with a medulloblastoma (Zhang 2015). STK11 Asp343Asn was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in 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 Asp343Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000213030 SCV000918291 uncertain significance not specified 2018-07-03 criteria provided, single submitter clinical testing Variant summary: STK11 c.1027G>A (p.Asp343Asn) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.7e-05 in 240152 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.1027G>A, has been reported in the literature in individuals as somatic events (Moens_2015, Wong_2015, Zhang_2015). 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. Five ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as "uncertain significance." Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000197027 SCV000254535 uncertain significance Peutz-Jeghers syndrome 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 343 of the STK11 protein (p.Asp343Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs368547224, ExAC 0.002%). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 140986). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
PreventionGenetics RCV000656982 SCV000806067 uncertain significance not provided 2017-08-25 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000213030 SCV000602203 uncertain significance not specified 2017-03-06 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000129286 SCV000788215 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-12 no assertion criteria provided 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.