Submissions for variant NM_000455.5(STK11):c.426C>T (p.Ser142=)

gnomAD frequency: 0.00053  dbSNP: rs758448869

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000162753	SCV000213229	likely benign	Hereditary cancer-predisposing syndrome	2014-09-02	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	RCV000990128	SCV000253253	benign	Peutz-Jeghers syndrome	2024-01-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162753	SCV000537425	likely benign	Hereditary cancer-predisposing syndrome	2016-02-10	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000588667	SCV000602223	benign	not provided	2023-05-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588667	SCV000696718	likely benign	not provided	2017-01-19	criteria provided, single submitter	clinical testing	Variant summary: The STK11 c.426C>T (p.Ser142Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 3/50790 control chromosomes at a frequency of 0.0000591, which is approximately 9 times the estimated maximal expected allele frequency of a pathogenic STK11 variant (0.0000063), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV000588667	SCV000806078	likely benign	not provided	2017-08-11	criteria provided, single submitter	clinical testing
Mendelics	RCV000990128	SCV001140937	likely benign	Peutz-Jeghers syndrome	2019-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000588667	SCV001852664	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000990128	SCV002057405	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588667	SCV002506226	likely benign	not provided	2022-01-26	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000162753	SCV002531693	benign	Hereditary cancer-predisposing syndrome	2020-11-01	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002465542	SCV002761018	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing