Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV001355139 | SCV001549929 | likely pathogenic | Generalized juvenile polyposis/juvenile polyposis coli | no assertion criteria provided | clinical testing | The STK11 c.291-?_464+?del variant (chr:19 g.1218416_1219412del GRCh37) results in a deletion of exons 2-3, although the precise breakpoints of this deletion were not determined, nor were the effects of this variant on the resulting mRNA or protein product determined. The variant was identified in 11 of 1354 proband chromosomes (frequency: 0.008) from individuals or families with Peutz-Jeghers Syndrome (Aretz 2005, Hearle 2006, Chow 2006, de Leng 2007, Hearle 2006, Orellana 2013, Papp 2010, Resta 2010, Yang 2010). The variant was also identified in ClinVar (classified as pathogenic by Invitae), Cosmic (3x in lung tissue), Zhejiang University Database (2x), and in Insight Hereditary Tumors Database (1x). The variant was not identified in dbSNP or the LOVD 3.0 database. The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). This variant is an in-frame deletion resulting in the removal of Exons 2-3, which are located in the catalytic domain of STK11 (Boudeau 2003). This region also includes a binding domain for Hsp90, which is regulates protein stability; inhibition of Hsp90-STK11 interaction results in protein degradation (Boudeau 2003). In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic. |