Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000663005 | SCV000786011 | likely pathogenic | Peutz-Jeghers syndrome | 2018-02-01 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800843 | SCV002046352 | likely pathogenic | not provided | 2021-05-19 | criteria provided, single submitter | clinical testing | This variant is located in a canonical splice-donor site and is predicted to interfere with normal STK11 mRNA splicing. To the best of our knowledge, the variant has not been reported in the published literature. Based on the available information, the variant is predicted to be likely pathogenic. |
| Invitae | RCV000663005 | SCV002305276 | uncertain significance | Peutz-Jeghers syndrome | 2022-10-13 | criteria provided, single submitter | clinical testing | 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. This sequence change falls in intron 2 of the STK11 gene. It does not directly change the encoded amino acid sequence of the STK11 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 548854). This variant affects a splice site of the intron 2, which has atypical splice donor sequences AT, instead of the canonical GT dinucleotides. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. |
| Ambry Genetics | RCV002343410 | SCV002621226 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-03 | criteria provided, single submitter | clinical testing | The c.374+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 2 in the STK11 gene. This nucleotide position is highly conserved in available vertebrate species. This alteration is located within a U12-type intron and in silico tools are not reliable predictors of splice sites in this type of intron. This alteration has been detected in individuals who do not have a personal or family history that is suggestive of Peutz-Jeghers Syndrome (Ambry internal data). RNA studies have demonstrated that this alteration results in a splice defect; the clinical impact of this abnormal splicing is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| All of Us Research Program, |
RCV000663005 | SCV004829270 | uncertain significance | Peutz-Jeghers syndrome | 2023-10-02 | criteria provided, single submitter | clinical testing | This variant disrupts a splice site and is predicted to result in abnormal splicing. Aberrant splicing and/or loss of function is an established mechanism of disease. This prediction has not been confirmed by functional studies. A different variant at the same splice site has been reported in association with disease and is independently classified as likely pathogenic or pathogenic. To date, the c.374+2T>C variant has not been reported in association with human disease in the medical literature. This variant is absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). |