Submissions for variant NM_000455.5(STK11):c.464+4C>T

gnomAD frequency: 0.00001  dbSNP: rs373167735

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000131463	SCV000186448	likely benign	Hereditary cancer-predisposing syndrome	2019-04-05	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae	RCV000204358	SCV000260487	likely benign	Peutz-Jeghers syndrome	2024-01-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000485485	SCV000567046	uncertain significance	not provided	2018-05-22	criteria provided, single submitter	clinical testing	This variant is denoted STK11 c.464+4C>T or IVS3+4C>T and consists of a C>T nucleotide substitution at the +4 position of intron 3 of the STK11 gene. In silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. STK11 c.464+4C>T was not observed in large population cohorts (Lek 2016). Based on currently available evidence, it is unclear whether STK11 c.464+4C>T is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color Diagnostics, LLC DBA Color Health	RCV000131463	SCV000686654	uncertain significance	Hereditary cancer-predisposing syndrome	2022-11-28	criteria provided, single submitter	clinical testing	This variant causes a C>T nucleotide substitution at the +4 position of intron 3 of the STK11 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. However, this prediction has not been confirmed in published RNA studies. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/187526 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.
PreventionGenetics, part of Exact Sciences	RCV003891668	SCV000806080	likely benign	STK11-related disorder	2023-05-22	criteria provided, single submitter	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).
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000485485	SCV002046744	uncertain significance	not provided	2023-01-05	criteria provided, single submitter	clinical testing	To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0000053 (1/187526 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant may affect proper STK11 mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant.
Genome-Nilou Lab	RCV000204358	SCV002057244	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000131463	SCV002531700	uncertain significance	Hereditary cancer-predisposing syndrome	2021-11-15	criteria provided, single submitter	curation
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492623	SCV004239725	uncertain significance	Breast and/or ovarian cancer	2023-01-17	criteria provided, single submitter	clinical testing