Submissions for variant NM_000455.5(STK11):c.766G>A (p.Glu256Lys)

dbSNP: rs1057520606

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001182876	SCV001348475	uncertain significance	Hereditary cancer-predisposing syndrome	2019-07-19	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with lysine at codon 256 of the STK11 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant 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). 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	RCV001295145	SCV001484058	uncertain significance	Peutz-Jeghers syndrome	2022-06-27	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 expected to disrupt STK11 protein function. ClinVar contains an entry for this variant (Variation ID: 922688). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 256 of the STK11 protein (p.Glu256Lys).
Genome-Nilou Lab	RCV001295145	SCV002057843	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001182876	SCV002673123	uncertain significance	Hereditary cancer-predisposing syndrome	2020-11-13	criteria provided, single submitter	clinical testing	The p.E256K variant (also known as c.766G>A), located in coding exon 6 of the STK11 gene, results from a G to A substitution at nucleotide position 766. The glutamic acid at codon 256 is replaced by lysine, 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.