Submissions for variant NM_000455.5(STK11):c.54G>T (p.Met18Ile)

dbSNP: rs755436889

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001024190	SCV001186162	uncertain significance	Hereditary cancer-predisposing syndrome	2019-09-13	criteria provided, single submitter	clinical testing	The p.M18I variant (also known as c.54G>T), located in coding exon 1 of the STK11 gene, results from a G to T substitution at nucleotide position 54. The methionine at codon 18 is replaced by isoleucine, an amino acid with highly 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.
Invitae	RCV001047448	SCV001211410	uncertain significance	Peutz-Jeghers syndrome	2023-04-03	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 18 of the STK11 protein (p.Met18Ile). ClinVar contains an entry for this variant (Variation ID: 825783). 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 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 not expected to disrupt STK11 protein function.
Genome-Nilou Lab	RCV001047448	SCV002057723	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001047448	SCV004834323	uncertain significance	Peutz-Jeghers syndrome	2023-12-13	criteria provided, single submitter	clinical testing	This missense variant replaces methionine with isoleucine at codon 18 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 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.