Submissions for variant NM_000455.5(STK11):c.317G>A (p.Arg106Gln)

gnomAD frequency: 0.00001  dbSNP: rs375622587

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000479549	SCV000569735	uncertain significance	not provided	2016-03-28	criteria provided, single submitter	clinical testing	This variant is denoted STK11 c.317G>A at the cDNA level, p.Arg106Gln (R106Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGG>CAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 Arg106Gln was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. STK11 Arg106Gln occurs at a position that is conserved in mammals and is located in the protein kinase domain (Uniprot). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether STK11 Arg106Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics	RCV000573267	SCV000675263	uncertain significance	Hereditary cancer-predisposing syndrome	2023-08-29	criteria provided, single submitter	clinical testing	The p.R106Q variant (also known as c.317G>A), located in coding exon 2 of the STK11 gene, results from a G to A substitution at nucleotide position 317. The arginine at codon 106 is replaced by glutamine, an amino acid with highly similar properties. This alteration was seen in 0/732 breast cancer patients, 1/189 colorectal cancer patients and 0/490 cancer-free elderly controls in a Turkish population (Akcay IM et al. Int J Cancer, 2021 01;148:285-295). 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.
Color Diagnostics, LLC DBA Color Health	RCV000573267	SCV000686631	uncertain significance	Hereditary cancer-predisposing syndrome	2023-11-24	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 106 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 been identified in an individual affected with colorectal cancer (PMID: 32658311). This variant has been identified in 3/249170 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.
Invitae	RCV000796866	SCV000936398	likely benign	Peutz-Jeghers syndrome	2023-08-17	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000796866	SCV002057770	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000796866	SCV004816339	uncertain significance	Peutz-Jeghers syndrome	2023-12-18	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 106 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 been identified in an individual affected with colorectal cancer (PMID: 32658311). This variant has been identified in 3/249170 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.