Submissions for variant NM_000455.5(STK11):c.17C>T (p.Pro6Leu)

dbSNP: rs775346785

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001213601	SCV001385238	uncertain significance	Peutz-Jeghers syndrome	2021-01-15	criteria provided, single submitter	clinical testing	This sequence change replaces proline with leucine at codon 6 of the STK11 protein (p.Pro6Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. 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. Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is not expected to disrupt STK11 protein function. This variant has not been reported in the literature in individuals with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 943418). This variant is not present in population databases (ExAC no frequency).
Color Diagnostics, LLC DBA Color Health	RCV001525629	SCV001735800	uncertain significance	Hereditary cancer-predisposing syndrome	2021-01-06	criteria provided, single submitter	clinical testing	This missense variant replaces proline with leucine at codon 6 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Genome-Nilou Lab	RCV001213601	SCV002057707	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001525629	SCV002715020	uncertain significance	Hereditary cancer-predisposing syndrome	2021-06-08	criteria provided, single submitter	clinical testing	The p.P6L variant (also known as c.17C>T), located in coding exon 1 of the STK11 gene, results from a C to T substitution at nucleotide position 17. The proline at codon 6 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.