Submissions for variant NM_000455.5(STK11):c.1109-4C>T

gnomAD frequency: 0.00001  dbSNP: rs1407794756

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001088020	SCV000629060	likely benign	Peutz-Jeghers syndrome	2024-01-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000572712	SCV000676284	likely benign	Hereditary cancer-predisposing syndrome	2019-06-06	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589586	SCV000696701	uncertain significance	not provided	2017-01-19	criteria provided, single submitter	clinical testing	Variant summary: The STK11 c.1109-4C>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 88156 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
PreventionGenetics, part of Exact Sciences	RCV000589586	SCV000806069	likely benign	not provided	2017-09-14	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000589586	SCV000888635	likely benign	not provided	2023-02-09	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000572712	SCV000912998	uncertain significance	Hereditary cancer-predisposing syndrome	2022-11-17	criteria provided, single submitter	clinical testing	This variant causes a C to T nucleotide substitution at the -4 position of intron 8 of the STK11 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/239174 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.
Genome-Nilou Lab	RCV001088020	SCV002057312	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000572712	SCV002531636	likely benign	Hereditary cancer-predisposing syndrome	2021-12-17	criteria provided, single submitter	curation
All of Us Research Program, National Institutes of Health	RCV001088020	SCV004816491	uncertain significance	Peutz-Jeghers syndrome	2023-09-04	criteria provided, single submitter	clinical testing	This variant causes a C to T nucleotide substitution at the -4 position of intron 8 of the STK11 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/239174 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.