ClinVar Miner

Submissions for variant NM_000455.5(STK11):c.375G>A (p.Met125Ile)

dbSNP: rs1421605142
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000816344 SCV000956845 uncertain significance Peutz-Jeghers syndrome 2019-03-30 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 125 of the STK11 protein (p.Met125Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. 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. 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. This variant has not been reported in the literature in individuals with STK11-related disease. This variant is not present in population databases (ExAC no frequency).
Ambry Genetics RCV001021067 SCV001182636 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-10 criteria provided, single submitter clinical testing The p.M125I variant (also known as c.375G>A) is located in coding exon 3 of the STK11 gene. The methionine at codon 125 is replaced by isoleucine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 3. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV001021067 SCV002052459 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-14 criteria provided, single submitter clinical testing This missense variant replaces methionine with isoleucine at codon 125 of the STK11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Genome-Nilou Lab RCV000816344 SCV002057779 uncertain significance Peutz-Jeghers syndrome 2021-07-15 criteria provided, single submitter clinical testing

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