ClinVar Miner

Submissions for variant NM_000455.5(STK11):c.662C>T (p.Pro221Leu)

gnomAD frequency: 0.00001  dbSNP: rs1167609100
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000776676 SCV000912301 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-23 criteria provided, single submitter clinical testing
Invitae RCV000803358 SCV000943224 uncertain significance Peutz-Jeghers syndrome 2023-11-13 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 221 of the STK11 protein (p.Pro221Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 30306255). ClinVar contains an entry for this variant (Variation ID: 630714). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt STK11 protein function with a positive predictive value of 95%. 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.
Ambry Genetics RCV000776676 SCV001187670 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-14 criteria provided, single submitter clinical testing The p.P221L variant (also known as c.662C>T), located in coding exon 5 of the STK11 gene, results from a C to T substitution at nucleotide position 662. The proline at codon 221 is replaced by leucine, an amino acid with similar properties. This variant was reported in a study of 192 Spanish breast and/or ovarian cancer families without mutations in BRCA1/2 (Bonache S et al. J. Cancer Res. Clin. Oncol. 2018 Dec;144:2495-2513). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Genome-Nilou Lab RCV000803358 SCV002057826 uncertain significance Peutz-Jeghers syndrome 2021-07-15 criteria provided, single submitter clinical testing

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