Submissions for variant NM_000455.5(STK11):c.537G>A (p.Pro179=)

dbSNP: rs528535500

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166943	SCV000217763	likely benign	Hereditary cancer-predisposing syndrome	2014-12-02	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.
GeneDx	RCV000441806	SCV000514795	benign	not specified	2015-08-14	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.
Invitae	RCV000473066	SCV000554118	likely benign	Peutz-Jeghers syndrome	2023-12-09	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477633	SCV000602228	likely benign	not provided	2023-01-16	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000166943	SCV000686661	likely benign	Hereditary cancer-predisposing syndrome	2016-04-27	criteria provided, single submitter	clinical testing
Counsyl	RCV000473066	SCV000786239	likely benign	Peutz-Jeghers syndrome	2018-03-26	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000473066	SCV002057412	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000166943	SCV002531708	likely benign	Hereditary cancer-predisposing syndrome	2022-03-10	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000473066	SCV004017934	benign	Peutz-Jeghers syndrome	2023-04-12	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	RCV000473066	SCV004816368	likely benign	Peutz-Jeghers syndrome	2023-05-31	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000473066	SCV001550798	likely benign	Peutz-Jeghers syndrome		no assertion criteria provided	clinical testing	The STK11 p.Pro179= variant was not identified in the literature nor was it identified in the LOVD 3.0, database. The variant was identified in dbSNP (rs528535500) as “with likely benign, other allele” and ClinVar (classified as likely benign by Invitae, Color, Ambry Genetics and 2 other submitters and benign by GeneDx). The variant was identified in control databases in 3 of 235,520 chromosomes at a frequency of 0.00001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 13,916 chromosomes (freq: 0.000072), East Asian in 1 of 17,286 chromosomes (freq: 0.00006), Finnish in 1 of 20,240 chromosomes (freq: 0.00005), while the variant was not observed in the Latino, Ashkenazi Jewish, European, Other and South Asian populations. The p.Pro179= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.