Submissions for variant NM_000455.5(STK11):c.299A>G (p.Gln100Arg)

gnomAD frequency: 0.00001  dbSNP: rs1060499957

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000468289	SCV000541130	uncertain significance	Peutz-Jeghers syndrome	2023-11-17	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 100 of the STK11 protein (p.Gln100Arg). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 403771). 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.
Ambry Genetics	RCV000569984	SCV000664320	uncertain significance	Hereditary cancer-predisposing syndrome	2024-02-22	criteria provided, single submitter	clinical testing	The p.Q100R variant (also known as c.299A>G), located in coding exon 2 of the STK11 gene, results from an A to G substitution at nucleotide position 299. The glutamine at codon 100 is replaced by arginine, an amino acid with highly 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001293537	SCV001482131	uncertain significance	not specified	2021-02-05	criteria provided, single submitter	clinical testing	Variant summary: STK11 c.299A>G (p.Gln100Arg) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 249120 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.299A>G in individuals affected with Peutz-Jeghers Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798818	SCV002042766	uncertain significance	Breast and/or ovarian cancer	2021-02-27	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000468289	SCV002057764	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003463836	SCV004205577	uncertain significance	Melanoma, cutaneous malignant, susceptibility to, 1	2023-07-13	criteria provided, single submitter	clinical testing