ClinVar

Description

This variant is denoted STK11 c.1256C>T at the cDNA level, p.Ser419Phe (S419F) at the protein level, and results in the change of a Serine to a Phenylalanine (TCC>TTC). This variant has not, to our knowledge, been published in the literature as a germline variant. STK11 Ser419Phe has been reported as a somatic variant in a melanoma patient-derived xenograft (Kemper 2016). This variant was not observed in approximately 6,500 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 Serine and Phenylalanine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. STK11 Ser419Phe occurs at a position that is not conserved and is located in the C-terminal 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 Ser419Phe is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.