Submissions for variant NM_000455.5(STK11):c.719C>T (p.Ser240Leu)

dbSNP: rs730881976

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001202671	SCV001373794	uncertain significance	Peutz-Jeghers syndrome	2023-10-20	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 240 of the STK11 protein (p.Ser240Leu). 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: 934310). 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.
Ambry Genetics	RCV002375130	SCV002672325	uncertain significance	Hereditary cancer-predisposing syndrome	2021-08-19	criteria provided, single submitter	clinical testing	The p.S240L variant (also known as c.719C>T), located in coding exon 5 of the STK11 gene, results from a C to T substitution at nucleotide position 719. The serine at codon 240 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics	RCV003462677	SCV004205602	uncertain significance	Melanoma, cutaneous malignant, susceptibility to, 1	2023-05-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV002375130	SCV004362397	uncertain significance	Hereditary cancer-predisposing syndrome	2023-09-06	criteria provided, single submitter	clinical testing	This missense variant replaces serine with leucine at codon 240 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 STK11-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same codon, c.719C>G (p.Ser240Trp), is considered to be disease-causing (ClinVar variation ID: 182902), suggesting that this position is important for the protein function. 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.
All of Us Research Program, National Institutes of Health	RCV001202671	SCV004818889	uncertain significance	Peutz-Jeghers syndrome	2023-10-02	criteria provided, single submitter	clinical testing	This missense variant replaces serine with leucine at codon 240 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 STK11-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same codon, c.719C>G (p.Ser240Trp), is considered to be disease-causing (ClinVar variation ID: 182902), suggesting that this position is important for the protein function. 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.