Submissions for variant NM_000455.5(STK11):c.357C>T (p.Asn119=)

gnomAD frequency: 0.00007  dbSNP: rs372511774

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000213010	SCV000211678	benign	not specified	2014-01-23	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000160969	SCV000213678	likely benign	Hereditary cancer-predisposing syndrome	2014-10-22	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.
Eurofins Ntd Llc (ga)	RCV000590217	SCV000227128	uncertain significance	not provided	2015-04-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000195629	SCV000253249	benign	Peutz-Jeghers syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000195629	SCV000410735	uncertain significance	Peutz-Jeghers syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Counsyl	RCV000195629	SCV000488905	likely benign	Peutz-Jeghers syndrome	2016-07-18	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000160969	SCV000686637	likely benign	Hereditary cancer-predisposing syndrome	2015-05-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590217	SCV000696716	benign	not provided	2016-09-30	criteria provided, single submitter	clinical testing	Variant summary: The STK11 c.357C>T (p.Asn119Asn) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predicting no significant impact on normal splicing. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 10/120328 (1/12032), which is approximately 13 times the estimated maximal expected allele frequency for a pathogenic STK11 variant 1/158730 (0.0000063), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories have classified this variant as benign/likely benign. One internal sample carrying this variant also carries another likely pathogenic variant RAD51C c.93delG, further supporting the benign outcome. Taken together, this variant is classified as Benign.
CeGaT Center for Human Genetics Tuebingen	RCV000590217	SCV001248462	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	STK11: BP4, BP7
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000213010	SCV001469914	benign	not specified	2020-04-20	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000590217	SCV001473727	likely benign	not provided	2019-11-24	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000195629	SCV002057237	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000213010	SCV002065598	likely benign	not specified	2020-12-18	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000160969	SCV002531685	benign	Hereditary cancer-predisposing syndrome	2021-04-29	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000195629	SCV004017956	benign	Peutz-Jeghers syndrome	2023-04-13	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
All of Us Research Program, National Institutes of Health	RCV000195629	SCV004816347	likely benign	Peutz-Jeghers syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000213010	SCV005089907	likely benign	not specified	2024-07-31	criteria provided, single submitter	clinical testing