Submissions for variant NM_000455.5(STK11):c.41A>G (p.Glu14Gly)

gnomAD frequency: 0.00002  dbSNP: rs750708224

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165124	SCV000215834	uncertain significance	Hereditary cancer-predisposing syndrome	2023-11-17	criteria provided, single submitter	clinical testing	The p.E14G variant (also known as c.41A>G), located in coding exon 1 of the STK11 gene, results from an A to G substitution at nucleotide position 41. The glutamic acid at codon 14 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV000632805	SCV000754000	uncertain significance	Peutz-Jeghers syndrome	2023-08-17	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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on STK11 protein function. ClinVar contains an entry for this variant (Variation ID: 185666). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is present in population databases (rs750708224, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 14 of the STK11 protein (p.Glu14Gly).
Color Diagnostics, LLC DBA Color Health	RCV000165124	SCV000910029	uncertain significance	Hereditary cancer-predisposing syndrome	2023-11-24	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with glycine at codon 14 of the STK11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 lung adenocarcinoma (PMID: 27060149). This variant has been identified in 4/233740 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	RCV000632805	SCV002057716	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
GeneDx	RCV003231348	SCV003929752	uncertain significance	not provided	2023-06-05	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
All of Us Research Program, National Institutes of Health	RCV000632805	SCV004816300	uncertain significance	Peutz-Jeghers syndrome	2023-12-18	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with glycine at codon 14 of the STK11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 lung adenocarcinoma (PMID: 27060149). This variant has been identified in 4/233740 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.