ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1217C>T (p.Ala406Val) (rs748202003)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204370 SCV000261236 uncertain significance Peutz-Jeghers syndrome 2018-11-05 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 406 of the STK11 protein (p.Ala406Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs748202003, ExAC 0.06%). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 220585). 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 valine 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 RCV000222032 SCV000279465 uncertain significance not provided 2015-10-02 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1217C>T at the cDNA level, p.Ala406Val (A406V) at the protein level, and results in the change of an Alanine to a Valine (GCG>GTG). This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. STK11 Ala406Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Alanine and Valine share similar properties, this is considered a conservative amino acid substitution. STK11 Ala406Val occurs at a position that is not conserved and is not located in a known functional domain (Hearle 2006). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether STK11 Ala406Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Counsyl RCV000204370 SCV000489233 uncertain significance Peutz-Jeghers syndrome 2016-09-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000565860 SCV000664325 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000565860 SCV000911545 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-30 criteria provided, single submitter clinical testing

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