ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.608C>T (p.Pro203Leu) (rs587782379)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131373 SCV000186349 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000219794 SCV000279960 uncertain significance not provided 2016-03-04 criteria provided, single submitter clinical testing This variant is denoted STK11 c.608C>T at the cDNA level, p.Pro203Leu (P203L) at the protein level, and results in the change of a Proline to a Leucine (CCG>CTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 Pro203Leu was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Proline and Leucine differ in some properties, this is considered a semi-conservative amino acid substitution. STK11 Pro203Leu occurs at a position that is conserved across species and is located in the 'binding of substrate and initiation of phospho transfer' domain (Hearle 2006). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether STK11 Pro203Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000536349 SCV000629131 uncertain significance Peutz-Jeghers syndrome 2017-07-05 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 203 of the STK11 protein (p.Pro203Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs587782379, ExAC 0.02%). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 142317). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. 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.
Color RCV000131373 SCV000910042 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-16 criteria provided, single submitter clinical testing

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