Submissions for variant NM_000455.5(STK11):c.838C>T (p.Pro280Ser)

dbSNP: rs1555738708

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001017674	SCV001178793	uncertain significance	Hereditary cancer-predisposing syndrome	2020-09-30	criteria provided, single submitter	clinical testing	The p.P280S variant (also known as c.838C>T), located in coding exon 6 of the STK11 gene, results from a C to T substitution at nucleotide position 838. The proline at codon 280 is replaced by serine, an amino acid with similar properties. This amino acid position is highly 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.
Invitae	RCV001061947	SCV001226714	uncertain significance	Peutz-Jeghers syndrome	2019-11-18	criteria provided, single submitter	clinical testing	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. 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 and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with STK11-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 280 of the STK11 protein (p.Pro280Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine.
Genome-Nilou Lab	RCV001061947	SCV002057853	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001017674	SCV004362402	uncertain significance	Hereditary cancer-predisposing syndrome	2022-09-19	criteria provided, single submitter	clinical testing	This missense variant replaces proline with serine at codon 280 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.