Submissions for variant NM_000455.5(STK11):c.31A>T (p.Met11Leu)

dbSNP: rs753834428

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000695432	SCV000823930	uncertain significance	Peutz-Jeghers syndrome	2022-03-04	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. 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. ClinVar contains an entry for this variant (Variation ID: 573702). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.001%). This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 11 of the STK11 protein (p.Met11Leu).
Ambry Genetics	RCV001019148	SCV001180471	uncertain significance	Hereditary cancer-predisposing syndrome	2022-07-11	criteria provided, single submitter	clinical testing	The p.M11L variant (also known as c.31A>T), located in coding exon 1 of the STK11 gene, results from an A to T substitution at nucleotide position 31. The methionine at codon 11 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is poorly 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.
Color Diagnostics, LLC DBA Color Health	RCV001019148	SCV001341005	uncertain significance	Hereditary cancer-predisposing syndrome	2022-11-17	criteria provided, single submitter	clinical testing	This missense variant replaces methionine with leucine at codon 11 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 1/226714 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.
Genome-Nilou Lab	RCV000695432	SCV002057712	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002268255	SCV002551914	uncertain significance	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University Hospital Muenster	RCV004584406	SCV002577853	uncertain significance	See cases	2021-12-17	criteria provided, single submitter	clinical testing	ACMG categories: PM1,PM2
All of Us Research Program, National Institutes of Health	RCV000695432	SCV004816299	uncertain significance	Peutz-Jeghers syndrome	2023-02-24	criteria provided, single submitter	clinical testing	This missense variant replaces methionine with leucine at codon 11 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 1/226714 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.