ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.464+4C>T (rs373167735)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131463 SCV000186448 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000204358 SCV000260487 uncertain significance Peutz-Jeghers syndrome 2018-12-26 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the STK11 gene. It does not directly change the encoded amino acid sequence of the STK11 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 142377). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, 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.
GeneDx RCV000485485 SCV000567046 uncertain significance not provided 2018-05-22 criteria provided, single submitter clinical testing This variant is denoted STK11 c.464+4C>T or IVS3+4C>T and consists of a C>T nucleotide substitution at the +4 position of intron 3 of the STK11 gene. In silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. STK11 c.464+4C>T was not observed in large population cohorts (Lek 2016). Based on currently available evidence, it is unclear whether STK11 c.464+4C>T is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000131463 SCV000686654 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-30 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000485485 SCV000806080 uncertain significance not provided 2017-06-29 criteria provided, single submitter clinical testing

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