Submissions for variant NM_000455.5(STK11):c.1243C>G (p.Arg415Gly)

dbSNP: rs864622448

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000206057	SCV000260679	uncertain significance	Peutz-Jeghers syndrome	2023-12-01	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 415 of the STK11 protein (p.Arg415Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 220264). 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 with a negative predictive value of 95%. 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.
GeneDx	RCV000759354	SCV000566529	uncertain significance	not provided	2023-09-18	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: 28900777)
Ambry Genetics	RCV000561859	SCV000664330	uncertain significance	Hereditary cancer-predisposing syndrome	2023-02-10	criteria provided, single submitter	clinical testing	The p.R415G variant (also known as c.1243C>G), located in coding exon 9 of the STK11 gene, results from a C to G substitution at nucleotide position 1243. The arginine at codon 415 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is highly 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759354	SCV000888640	uncertain significance	not provided	2018-03-27	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765435	SCV000896719	uncertain significance	Carcinoma of pancreas; Peutz-Jeghers syndrome; Malignant tumor of testis	2018-10-31	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000561859	SCV000906764	uncertain significance	Hereditary cancer-predisposing syndrome	2023-03-16	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glycine at codon 415 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.
Genome-Nilou Lab	RCV000206057	SCV002057985	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003468946	SCV004205553	uncertain significance	Melanoma, cutaneous malignant, susceptibility to, 1	2023-09-21	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000206057	SCV004819018	uncertain significance	Peutz-Jeghers syndrome	2023-12-18	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glycine at codon 415 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.