ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.597+1G>T (rs886039554)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000254989 SCV000322375 pathogenic not provided 2016-10-28 criteria provided, single submitter clinical testing The c.597+1 G>T splice site variant in the STK11 gene has been previously reported in association with Peutz-Jeghers syndrome (Mehenni et al., 2006). This variant destroys the canonical splice donor site in intron 4, and is expected to cause abnormal gene splicing. The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, this variant is pathogenic.
Ambry Genetics RCV000492737 SCV000580933 likely pathogenic Hereditary cancer-predisposing syndrome 2013-12-20 criteria provided, single submitter clinical testing Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Invitae RCV000700997 SCV000829777 pathogenic Peutz-Jeghers syndrome 2018-03-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the STK11 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in at least one individual affected with Peutz-Jeghers syndrome (PMID: 16407375). The variant is also known as IVS4+1G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 265451). A different variant affecting this nucleotide (c.597+1G>A) has been determined to be pathogenic (PMID: 21118512). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in STK11 are known to be pathogenic (PMID: 15188174, 16287113). For these reasons, this variant has been classified as Pathogenic.

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