Submissions for variant NM_000455.5(STK11):c.1093G>A (p.Asp365Asn)

dbSNP: rs1599929572

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000823045	SCV000963883	uncertain significance	Peutz-Jeghers syndrome	2023-03-07	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: 664864). 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 aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 365 of the STK11 protein (p.Asp365Asn).
Color Diagnostics, LLC DBA Color Health	RCV001182547	SCV001348020	uncertain significance	Hereditary cancer-predisposing syndrome	2020-07-13	criteria provided, single submitter	clinical testing	This missense variant replaces aspartic acid with asparagine at codon 365 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 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.
Genome-Nilou Lab	RCV000823045	SCV002057923	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001182547	SCV002733096	uncertain significance	Hereditary cancer-predisposing syndrome	2022-06-11	criteria provided, single submitter	clinical testing	The p.D365N variant (also known as c.1093G>A), located in coding exon 8 of the STK11 gene, results from a G to A substitution at nucleotide position 1093. The aspartic acid at codon 365 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
All of Us Research Program, National Institutes of Health	RCV000823045	SCV004818980	uncertain significance	Peutz-Jeghers syndrome	2023-09-05	criteria provided, single submitter	clinical testing	This missense variant replaces aspartic acid with asparagine at codon 365 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 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.