ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.971C>T (p.Pro324Leu) (rs367807476)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000123070 SCV000166365 uncertain significance Peutz-Jeghers syndrome 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 324 of the STK11 protein (p.Pro324Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs367807476, ExAC 0.04%). This variant has been reported in an individual affected with Peutz–Jeghers syndrome (PJS) (PMID: 10780518 ). ClinVar contains an entry for this variant (Variation ID: 135931). Experimental studies have shown that this missense change decreases STK11-mediated activation of the AMP-activated protein kinase (AMPK) and impairs downstream signaling (PMID: 19892943, 15800014), but does not disrupt STK11 kinase activity or interfere with STK11-induced growth arrest. However, The clinical impact of these findings has not been determined. 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 RCV000163389 SCV000213929 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
CSER_CC_NCGL; University of Washington Medical Center RCV000123070 SCV000190635 uncertain significance Peutz-Jeghers syndrome 2014-06-01 no assertion criteria provided research
Database of Curated Mutations (DoCM) RCV000123070 SCV000510425 likely pathogenic Peutz-Jeghers syndrome 2016-05-13 no assertion criteria provided literature only

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