Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000813934 | SCV000954318 | uncertain significance | Peutz-Jeghers syndrome | 2022-09-17 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 657344). This variant has been observed in individual(s) with colorectal cancer (PMID: 28135145). This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 97 of the STK11 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the STK11 protein. It affects a nucleotide within the consensus splice site. |
| Ambry Genetics | RCV003307517 | SCV003999540 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-21 | criteria provided, single submitter | clinical testing | The c.291G>A variant (also known as p.K97K), located in coding exon 2 of the STK11 gene, results from a G to A substitution at nucleotide position 291. This variant has been reported in an individual affected with colorectal cancer (Yurgelun MB et al. J Clin Oncol, 2017 Apr;35:1086-1095). This nucleotide substitution does not change the lysine at codon 97. However, this change occurs in the first base pair of coding exon 2, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may result in the creation or strengthening of a novel splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |