Submissions for variant NM_000455.5(STK11):c.1195C>A (p.Gln399Lys)

gnomAD frequency: 0.00001  dbSNP: rs1060499968

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000458053	SCV000541160	uncertain significance	Peutz-Jeghers syndrome	2023-11-13	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 399 of the STK11 protein (p.Gln399Lys). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 403791). 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.
Color Diagnostics, LLC DBA Color Health	RCV000579669	SCV000686604	uncertain significance	Hereditary cancer-predisposing syndrome	2023-07-24	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with lysine at codon 399 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 3/227502 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.
Fulgent Genetics, Fulgent Genetics	RCV000765434	SCV000896718	uncertain significance	Carcinoma of pancreas; Peutz-Jeghers syndrome; Malignant tumor of testis	2018-10-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000579669	SCV001170333	uncertain significance	Hereditary cancer-predisposing syndrome	2023-07-22	criteria provided, single submitter	clinical testing	The p.Q399K variant (also known as c.1195C>A), located in coding exon 9 of the STK11 gene, results from a C to A substitution at nucleotide position 1195. The glutamine at codon 399 is replaced by lysine, an amino acid with 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	RCV000458053	SCV002057965	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
GeneDx	RCV004591284	SCV005078949	uncertain significance	not provided	2024-01-03	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)