Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000227440 | SCV000284867 | likely benign | Peutz-Jeghers syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV001179584 | SCV001344282 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-01 | criteria provided, single submitter | clinical testing | This variant deletes a nucleotide at the +8 position of intron 3 of the STK11 gene. Splice site prediction tools are inconclusive regarding the impact of this variant on RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/183100 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001420890 | SCV001623326 | uncertain significance | not specified | 2021-04-25 | criteria provided, single submitter | clinical testing | Variant summary: STK11 c.464+8delC alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.1e-05 in 183100 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.464+8delC in individuals affected with Peutz-Jeghers Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Genome- |
RCV000227440 | SCV002057245 | likely benign | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing |