Submissions for variant NM_000455.5(STK11):c.56C>T (p.Ser19Leu)

dbSNP: rs1426026332

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000663263	SCV000786492	uncertain significance	Peutz-Jeghers syndrome	2018-05-15	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000777388	SCV000913250	uncertain significance	Hereditary cancer-predisposing syndrome	2022-12-12	criteria provided, single submitter	clinical testing	This missense variant replaces serine with leucine at codon 19 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 STK11-related disorders in the literature. This variant has been identified in 1/241614 chromosomes 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.
Ambry Genetics	RCV000777388	SCV001186441	uncertain significance	Hereditary cancer-predisposing syndrome	2021-12-02	criteria provided, single submitter	clinical testing	The p.S19L variant (also known as c.56C>T), located in coding exon 1 of the STK11 gene, results from a C to T substitution at nucleotide position 56. The serine at codon 19 is replaced by leucine, an amino acid with dissimilar properties. This alteration was detected in a cohort of 35 endometrial cancer patients who also had a mismatch repair (MMR) pathogenic mutation (J&oacute;ri B et al. Oncotarget, 2015 Dec;6:41108-22). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV000663263	SCV002057725	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Invitae	RCV000663263	SCV003442544	uncertain significance	Peutz-Jeghers syndrome	2022-09-10	criteria provided, single submitter	clinical testing	This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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. ClinVar contains an entry for this variant (Variation ID: 548908). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 19 of the STK11 protein (p.Ser19Leu).
Myriad Genetics, Inc.	RCV000663263	SCV004017951	uncertain significance	Peutz-Jeghers syndrome	2023-04-12	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
All of Us Research Program, National Institutes of Health	RCV000663263	SCV004816304	uncertain significance	Peutz-Jeghers syndrome	2023-08-15	criteria provided, single submitter	clinical testing	This missense variant replaces serine with leucine at codon 19 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 STK11-related disorders in the literature. This variant has been identified in 1/241614 chromosomes 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.