ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1012G>A (p.Val338Met) (rs587782302)

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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 RCV000131186 SCV000186135 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Invitae RCV000168376 SCV000219067 uncertain significance Peutz-Jeghers syndrome 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 338 of the STK11 protein (p.Val338Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs587782302, ExAC 0.007%). This variant has been observed in an individual affected with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 142198). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
GeneDx RCV000222337 SCV000279260 uncertain significance not provided 2018-07-19 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1012G>A at the cDNA level, p.Val338Met (V338M) at the protein level, and results in the change of a Valine to a Methionine (GTG>ATG). This variant has been reported in an individual with colon cancer who also carried a pathogenic BRCA2 variant (Yurgelun 2017). STK11 Val338Met was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. 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 Val338Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000168376 SCV000489083 uncertain significance Peutz-Jeghers syndrome 2016-08-15 criteria provided, single submitter clinical testing
Color RCV000131186 SCV000686573 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000222337 SCV000888633 uncertain significance not provided 2017-09-19 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765433 SCV000896717 uncertain significance Carcinoma of pancreas; Peutz-Jeghers syndrome; Malignant tumor of testis 2018-10-31 criteria provided, single submitter clinical testing

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