Submissions for variant NM_000455.5(STK11):c.1088C>T (p.Thr363Ile)

gnomAD frequency: 0.00004  dbSNP: rs587778695

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000206210	SCV000259712	likely benign	Peutz-Jeghers syndrome	2024-01-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000219976	SCV000277985	benign	Hereditary cancer-predisposing syndrome	2023-04-19	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Counsyl	RCV000206210	SCV000489312	uncertain significance	Peutz-Jeghers syndrome	2016-09-16	criteria provided, single submitter	clinical testing
GeneDx	RCV000656983	SCV000565599	uncertain significance	not provided	2019-12-09	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in individuals with Peutz-Jehgers syndrome and individuals with breast cancer as well as in healthy controls (Wei 2011, Liu 2012, Bodian 2014, Tung 2015, Xie 2018); This variant is associated with the following publications: (PMID: 25186627, 24728327, 22216297, 24652667, 22942091, 28580595)
Color Diagnostics, LLC DBA Color Health	RCV000219976	SCV000691466	likely benign	Hereditary cancer-predisposing syndrome	2023-10-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000219976	SCV002531631	likely benign	Hereditary cancer-predisposing syndrome	2020-12-30	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000206210	SCV004017984	uncertain significance	Peutz-Jeghers syndrome	2023-04-14	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
All of Us Research Program, National Institutes of Health	RCV000206210	SCV004818978	likely benign	Peutz-Jeghers syndrome	2024-02-05	criteria provided, single submitter	clinical testing	This missense variant replaces threonine with isoleucine at codon 363 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individuals affected with Peutz-Jeghers syndrome (PMID: 22942091) and breast cancer (PMID: 25186627). This variant has been identified in 25/275702 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.
ITMI	RCV000122092	SCV000086307	not provided	not specified	2013-09-19	no assertion provided	reference population
Database of Curated Mutations (DoCM)	RCV000206210	SCV000510522	likely pathogenic	Peutz-Jeghers syndrome	2016-05-13	no assertion criteria provided	literature only