ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.617C>T (p.Ala206Val) (rs764244639)

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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 RCV000163146 SCV000213663 uncertain significance Hereditary cancer-predisposing syndrome 2016-05-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000412198 SCV000488269 uncertain significance Peutz-Jeghers syndrome 2016-02-10 criteria provided, single submitter clinical testing
GeneDx RCV000478878 SCV000566068 uncertain significance not provided 2016-08-19 criteria provided, single submitter clinical testing This variant is denoted STK11 c.617C>T at the cDNA level, p.Ala206Val (A206V) 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 pathogenic or benign. STK11 Ala206Val was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting 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 Ala206Val occurs at a position that is not conserved across species and is located in the protein kinase domain and within the domains responsible for binding of substrate and initiation of phospho transfer (Hearle 2006, UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether STK11 Ala206Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000412198 SCV000629133 uncertain significance Peutz-Jeghers syndrome 2018-02-09 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 206 of the STK11 protein (p.Ala206Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs764244639, ExAC 0.004%) but has not been reported in the literature in individuals with a STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 184032). 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000163146 SCV000911131 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-24 criteria provided, single submitter clinical testing

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