ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.875A>T (p.Tyr292Phe) (rs587780011)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115602 SCV000149511 uncertain significance not provided 2014-02-26 criteria provided, single submitter clinical testing This variant is denoted STK11 c.875A>T at the cDNA level, p.Tyr292Phe (Y292F) at the protein level, and results in the change of a Tyrosine to a Phenylalanine (TAC>TTC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 Tyr292Phe 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 Tyrosine and Phenylalanine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution and is likely to affect protein integrity. STK11 Tyr292Phe occurs at a position that is well conserved across species and is located in the Protein Kinase domain (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether STK11 Tyr292Phe is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000214773 SCV000273899 uncertain significance Hereditary cancer-predisposing syndrome 2015-02-16 criteria provided, single submitter clinical testing
Invitae RCV000559287 SCV000629153 uncertain significance Peutz-Jeghers syndrome 2018-12-31 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with phenylalanine at codon 292 of the STK11 protein (p.Tyr292Phe). The tyrosine residue is moderately conserved and there is a small physicochemical difference between tyrosine and phenylalanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 127706). 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. 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.

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