Submissions for variant NM_000455.5(STK11):c.22C>G (p.Gln8Glu)

dbSNP: rs760588289

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000632809	SCV000754004	uncertain significance	Peutz-Jeghers syndrome	2022-09-06	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: 527816). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is present in population databases (rs760588289, gnomAD 0.001%). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 8 of the STK11 protein (p.Gln8Glu).
Ambry Genetics	RCV001015109	SCV001175905	uncertain significance	Hereditary cancer-predisposing syndrome	2018-09-25	criteria provided, single submitter	clinical testing	The p.Q8E variant (also known as c.22C>G), located in coding exon 1 of the STK11 gene, results from a C to G substitution at nucleotide position 22. The glutamine at codon 8 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is not well 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.
Genome-Nilou Lab	RCV000632809	SCV002057709	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001015109	SCV004362375	uncertain significance	Hereditary cancer-predisposing syndrome	2023-07-24	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with glutamic acid at codon 8 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 STK11-related disorders in the literature. This variant has been identified in 1/215880 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.
All of Us Research Program, National Institutes of Health	RCV000632809	SCV004825132	uncertain significance	Peutz-Jeghers syndrome	2023-08-15	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with glutamic acid at codon 8 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 STK11-related disorders in the literature. This variant has been identified in 1/215880 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.