Submissions for variant NM_000455.5(STK11):c.49C>G (p.Leu17Val)

gnomAD frequency: 0.00001  dbSNP: rs780581573

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000526066	SCV000629119	uncertain significance	Peutz-Jeghers syndrome	2024-01-02	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 17 of the STK11 protein (p.Leu17Val). This variant is present in population databases (rs780581573, gnomAD 0.009%). 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: 458049). 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. 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.
Color Diagnostics, LLC DBA Color Health	RCV000774552	SCV000908264	uncertain significance	Hereditary cancer-predisposing syndrome	2019-02-28	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000526066	SCV002057720	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000774552	SCV002641766	uncertain significance	Hereditary cancer-predisposing syndrome	2022-03-28	criteria provided, single submitter	clinical testing	The p.L17V variant (also known as c.49C>G), located in coding exon 1 of the STK11 gene, results from a C to G substitution at nucleotide position 49. The leucine at codon 17 is replaced by valine, an amino acid with highly similar 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.
All of Us Research Program, National Institutes of Health	RCV000526066	SCV004816303	uncertain significance	Peutz-Jeghers syndrome	2023-12-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV004568747	SCV005052876	uncertain significance	Melanoma, cutaneous malignant, susceptibility to, 1	2024-02-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003983109	SCV004800328	uncertain significance	STK11-related disorder	2024-02-27	no assertion criteria provided	clinical testing	The STK11 c.49C>G variant is predicted to result in the amino acid substitution p.Leu17Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0088% of alleles in individuals of African descent in gnomAD. This variant is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/458049/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.