ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.992G>A (p.Arg331Gln) (rs371264852)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130707 SCV000185594 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000199024 SCV000254562 uncertain significance Peutz-Jeghers syndrome 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 331 of the STK11 protein (p.Arg331Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs371264852, ExAC 0.01%). This variant has been reported in an individual affected with colon cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 141962). 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.
Counsyl RCV000199024 SCV000488391 uncertain significance Peutz-Jeghers syndrome 2016-03-15 criteria provided, single submitter clinical testing
GeneDx RCV000486850 SCV000565598 uncertain significance not provided 2018-12-19 criteria provided, single submitter clinical testing This variant is denoted STK11 c.992G>A at the cDNA level, p.Arg331Gln (R331Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGG>CAG). This variant has been observed in at least one individual with breast cancer, and in one individual with colon cancer who also carried a pathogenic MLH1 variant (Yurgelun 2017, Momozawa 2018). STK11 Arg331Gln was not observed at a significant allele frequency in large population cohorts (Lek 2016). STK11 Arg331Gln is located in the C-terminal region (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 Arg331Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000130707 SCV000902884 likely benign Hereditary cancer-predisposing syndrome 2016-02-29 criteria provided, single submitter clinical testing
Mendelics RCV000199024 SCV001140946 uncertain significance Peutz-Jeghers syndrome 2019-05-28 criteria provided, single submitter clinical testing
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761149 SCV000891065 uncertain significance Retinoblastoma 2017-02-15 no assertion criteria provided clinical testing

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