Submissions for variant NM_000455.5(STK11):c.-1C>T

gnomAD frequency: 0.00001  dbSNP: rs759284466

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164494	SCV000215143	uncertain significance	Hereditary cancer-predisposing syndrome	2023-06-08	criteria provided, single submitter	clinical testing	The c.-1C>T variant is located in the 5' untranslated region (5’ UTR) of the STK11 gene. This variant results from a C to T substitution 1 bases upstream from the first translated codon. This alteration was identified in a cohort of 1260 individuals undergoing panel testing for Lynch syndrome due to having a diagnosis of a Lynch-associated cancer and/or polyps (Yurgelun MB et al. Gastroenterology, 2015 Sep;149:604-13.e20). This nucleotide position is poorly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx	RCV000986036	SCV000523220	likely benign	not provided	2018-09-26	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25980754)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000431625	SCV000920285	uncertain significance	not specified	2018-12-07	criteria provided, single submitter	clinical testing	Variant summary: STK11 c.-1C>T is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 1.1e-05 in 182860 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.-1C>T has been reported in the literature in individuals affected with Lynch syndrome associated cancer (Yurgelun_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Peutz-Jeghers Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000986036	SCV001134839	uncertain significance	not provided	2019-08-16	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000164494	SCV001341888	likely benign	Hereditary cancer-predisposing syndrome	2015-04-13	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001808438	SCV002057224	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003491893	SCV004239718	uncertain significance	Breast and/or ovarian cancer	2022-09-28	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004745242	SCV005363947	likely benign	STK11-related disorder	2024-07-24	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).