Submissions for variant NM_000455.5(STK11):c.679G>A (p.Gly227Ser)

dbSNP: rs1599926923

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000797980	SCV000937571	uncertain significance	Peutz-Jeghers syndrome	2022-12-20	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 expected to disrupt STK11 protein function. ClinVar contains an entry for this variant (Variation ID: 644132). 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 glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 227 of the STK11 protein (p.Gly227Ser).
Ambry Genetics	RCV001025659	SCV001187897	uncertain significance	Hereditary cancer-predisposing syndrome	2020-10-16	criteria provided, single submitter	clinical testing	The p.G227S variant (also known as c.679G>A), located in coding exon 5 of the STK11 gene, results from a G to A substitution at nucleotide position 679. The glycine at codon 227 is replaced by serine, an amino acid with similar 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.
Color Diagnostics, LLC DBA Color Health	RCV001025659	SCV001341736	uncertain significance	Hereditary cancer-predisposing syndrome	2019-10-31	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with serine at codon 227 of the STK11 protein. Computational prediction tool suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold ≥0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001800885	SCV002047147	uncertain significance	not provided	2021-05-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000797980	SCV002057830	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000797980	SCV004818885	uncertain significance	Peutz-Jeghers syndrome	2024-02-05	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with serine at codon 227 of the STK11 protein. Computational prediction tool suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >=0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed 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.