Submissions for variant NM_000455.5(STK11):c.552C>T (p.Leu184=)

gnomAD frequency: 0.00003  dbSNP: rs587780719

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084776	SCV000166357	likely benign	Peutz-Jeghers syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000164592	SCV000215251	likely benign	Hereditary cancer-predisposing syndrome	2014-05-22	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000123062	SCV000602229	benign	not provided	2019-03-22	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000164592	SCV000686662	likely benign	Hereditary cancer-predisposing syndrome	2015-07-17	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000507150	SCV000918286	benign	not specified	2018-02-16	criteria provided, single submitter	clinical testing	Variant summary: STK11 c.552C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.3e-05 in 265506 control chromosomes (gnomAD). The observed variant frequency is approximately 3.62 fold of the estimated maximal expected allele frequency for a pathogenic variant in STK11 causing Peutz-Jeghers Syndrome phenotype (6.3e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.552C>T in individuals affected with Peutz-Jeghers Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV000123062	SCV001935862	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001084776	SCV002057413	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000507150	SCV004242946	likely benign	not specified	2024-02-06	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001084776	SCV004816371	likely benign	Peutz-Jeghers syndrome	2024-02-05	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003945109	SCV004762509	likely benign	STK11-related disorder	2019-10-31	no assertion criteria provided	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).