ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1038C>T (p.Gly346=) (rs767565606)

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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 RCV000163139 SCV000213655 likely benign Hereditary cancer-predisposing syndrome 2015-02-09 criteria provided, single submitter clinical testing
Color RCV000163139 SCV000691463 likely benign Hereditary cancer-predisposing syndrome 2016-04-27 criteria provided, single submitter clinical testing
Counsyl RCV000198223 SCV000784886 likely benign Peutz-Jeghers syndrome 2017-01-27 criteria provided, single submitter clinical testing
GeneDx RCV000427198 SCV000519100 likely benign not specified 2017-08-15 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.
Integrated Genetics/Laboratory Corporation of America RCV000427198 SCV000920281 uncertain significance not specified 2018-05-11 criteria provided, single submitter clinical testing Variant summary: STK11 c.1038C>T alters a non-conserved nucleotide resulting in a synonymous change. Several computational tools predict a significant impact on normal splicing: Five predict the variant creates a cryptic donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.1e-05 in 93998 control chromosomes. The observed variant frequency is approximately 3.4 fold of the estimated maximal expected allele frequency for a pathogenic variant in STK11 causing Peutz-Jeghers Syndrome phenotype (6.3e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1038C>T in individuals affected with Peutz-Jeghers Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (3 LB and 2 VUS). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Invitae RCV000198223 SCV000254536 uncertain significance Peutz-Jeghers syndrome 2018-06-29 criteria provided, single submitter clinical testing This sequence change affects codon 346 of the STK11 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the STK11 protein. This variant is present in population databases (rs767565606, 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: 184026). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV000198223 SCV000839424 uncertain significance Peutz-Jeghers syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000427198 SCV000602204 uncertain significance not specified 2017-05-20 criteria provided, single submitter clinical testing

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