ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1168G>A (p.Val390Met) (rs374078532)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131310 SCV000186282 uncertain significance Hereditary cancer-predisposing syndrome 2015-08-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
GeneDx RCV000482811 SCV000572613 uncertain significance not provided 2016-12-29 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1168G>A at the cDNA level, p.Val390Met (V390M) at the protein level, and results in the change of a Valine to a Methionine (GTG>ATG). This variant has not, to our knowledge, been published in the literature as either a pathogenic germline variant or a benign polymorphism. However, it has been reported as a somatic variant in a lung adenocarcinoma (Kim 2014). STK11 Val390Met was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Valine and Methionine share similar properties, this is considered a conservative amino acid substitution. STK11 Val390Met occurs at a position where amino acids with properties similar to Valine are tolerated across species and is not located in a known functional domain (Hearle 2006). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether STK11 Val390Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000536228 SCV000629071 uncertain significance Peutz-Jeghers syndrome 2018-05-31 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 390 of the STK11 protein (p.Val390Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs374078532, ExAC 0.01%). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 142283). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; 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.
Counsyl RCV000536228 SCV000786457 uncertain significance Peutz-Jeghers syndrome 2018-05-04 criteria provided, single submitter clinical testing
Color RCV000131310 SCV000910062 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-30 criteria provided, single submitter clinical testing

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