Submissions for variant NM_000455.5(STK11):c.812G>A (p.Ser271Asn)

dbSNP: rs1599927654

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001027203	SCV001189721	uncertain significance	Hereditary cancer-predisposing syndrome	2023-09-05	criteria provided, single submitter	clinical testing	The p.S271N variant (also known as c.812G>A), located in coding exon 6 of the STK11 gene, results from a G to A substitution at nucleotide position 812. The serine at codon 271 is replaced by asparagine, 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.
Invitae	RCV001368925	SCV001565347	uncertain significance	Peutz-Jeghers syndrome	2023-08-28	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 827468). 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. 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 serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 271 of the STK11 protein (p.Ser271Asn).
Genome-Nilou Lab	RCV001368925	SCV002057846	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
GeneDx	RCV002067710	SCV002496210	uncertain significance	not provided	2022-03-29	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter 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)
Sema4, Sema4	RCV001027203	SCV002526941	uncertain significance	Hereditary cancer-predisposing syndrome	2021-09-20	criteria provided, single submitter	curation
Color Diagnostics, LLC DBA Color Health	RCV001027203	SCV004362401	uncertain significance	Hereditary cancer-predisposing syndrome	2021-11-12	criteria provided, single submitter	clinical testing	This missense variant replaces serine with asparagine at codon 271 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.
All of Us Research Program, National Institutes of Health	RCV001368925	SCV004818911	uncertain significance	Peutz-Jeghers syndrome	2024-01-11	criteria provided, single submitter	clinical testing	This missense variant replaces serine with asparagine at codon 271 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.