ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1283C>T (p.Ser428Leu) (rs587781537)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000218637 SCV000279226 uncertain significance not provided 2018-11-20 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1283C>T at the cDNA level, p.Ser428Leu (S428L) at the protein level, and results in the change of a Serine to a Leucine (TCG>TTG). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. STK11 Ser428Leu was not observed in large population cohorts (Lek 2016). This variant is located in the c-terminal domain (Daniell 2017). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether STK11 Ser428Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000476552 SCV000541128 uncertain significance Peutz-Jeghers syndrome 2018-11-07 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 428 of the STK11 protein (p.Ser428Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. While this variant is present in population databases (rs587781537), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 234438). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000567419 SCV000672309 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or Conflicting Evidence,in silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Color RCV000567419 SCV000686616 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-29 criteria provided, single submitter clinical testing

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