Submissions for variant NM_000455.5(STK11):c.337C>G (p.Leu113Val)

dbSNP: rs1555737432

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000584425	SCV000691497	uncertain significance	Hereditary cancer-predisposing syndrome	2022-03-30	criteria provided, single submitter	clinical testing	This missense variant replaces leucine with valine at codon 113 of the STK11 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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.
Ambry Genetics	RCV000584425	SCV001181581	uncertain significance	Hereditary cancer-predisposing syndrome	2018-03-22	criteria provided, single submitter	clinical testing	The p.L113V variant (also known as c.337C>G), located in coding exon 2 of the STK11 gene, results from a C to G substitution at nucleotide position 337. The leucine at codon 113 is replaced by valine, an amino acid with highly similar properties. 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	RCV001809682	SCV002057775	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Invitae	RCV001809682	SCV002273629	uncertain significance	Peutz-Jeghers syndrome	2022-05-19	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 113 of the STK11 protein (p.Leu113Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 492524). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt STK11 protein function. 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.
GeneDx	RCV004592895	SCV005080875	uncertain significance	not provided	2023-08-08	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15863673)