ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.425G>A (p.Ser142Asn) (rs1568705518)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000781893 SCV000920279 uncertain significance not specified 2018-03-30 criteria provided, single submitter clinical testing Variant summary: STK11 c.425G>A (p.Ser142Asn) results in a conservative amino acid change located in the Protein kinase domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 50790 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.425G>A in individuals affected with Peutz-Jeghers Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. An internal sample reports the variant to co-occur with a likely pathogenic MLH1 variant, c.980_983dupAGCA (p.His329fsX34). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000797412 SCV000936967 uncertain significance Peutz-Jeghers syndrome 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 142 of the STK11 protein (p.Ser142Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with STK11-related conditions. 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 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.

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