ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1108+3G>A (rs755746417)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230024 SCV000284842 likely benign Peutz-Jeghers syndrome 2020-12-03 criteria provided, single submitter clinical testing
GeneDx RCV000445130 SCV000532358 likely benign not specified 2018-02-14 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000445130 SCV000602206 likely benign not specified 2017-07-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV000561129 SCV000664353 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-13 criteria provided, single submitter clinical testing The c.1108+3G>A intronic variant results from a G to A substitution 3 nucleotides after coding exon 8 in the STK11 gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Health, Inc RCV000561129 SCV000691471 likely benign Hereditary cancer-predisposing syndrome 2017-08-20 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000445130 SCV000918288 uncertain significance not specified 2018-06-04 criteria provided, single submitter clinical testing Variant summary: STK11 c.1108+3G>A alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.1e-05 in 237544 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1108+3G>A in individuals affected with Peutz-Jeghers Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign (3x) and uncertain significance (2x). Based on the evidence outlined above, the variant was classified as uncertain significance.

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