ClinVar Miner

Submissions for variant NM_000455.5(STK11):c.464+1G>A

dbSNP: rs730881971
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001185859 SCV001352168 likely pathogenic Hereditary cancer-predisposing syndrome 2020-05-04 criteria provided, single submitter clinical testing This variant causes a G to A nucleotide substitution at the +1 position of intron 3 of the STK11 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with Peutz-Jeghers syndrome with positive family history (PMID 30528796). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of STK11 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic.
Invitae RCV001377432 SCV001574763 pathogenic Peutz-Jeghers syndrome 2023-07-25 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 of the STK11 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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). Disruption of this splice site has been observed in individuals with Peutz-Jeghers syndrome (PMID: 30528796; Invitae). ClinVar contains an entry for this variant (Variation ID: 924495). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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