Submissions for variant NM_000455.5(STK11):c.480G>T (p.Leu160=)

gnomAD frequency: 0.00001  dbSNP: rs1176365465

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000605163	SCV000719833	likely benign	not specified	2017-05-26	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000934535	SCV001080258	likely benign	Peutz-Jeghers syndrome	2023-09-10	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001177845	SCV001342126	likely benign	Hereditary cancer-predisposing syndrome	2017-12-05	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001177845	SCV002531706	likely benign	Hereditary cancer-predisposing syndrome	2021-09-14	criteria provided, single submitter	curation
Ambry Genetics	RCV001177845	SCV002633972	likely benign	Hereditary cancer-predisposing syndrome	2020-01-24	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.
All of Us Research Program, National Institutes of Health	RCV000934535	SCV004816365	likely benign	Peutz-Jeghers syndrome	2023-06-28	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356159	SCV001551247	likely benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The STK11 p.Leu160= variant was not identified in the literature nor was it identified in the dbSNP, Cosmic, LOVD 3.0, Zhejiang University Database, or Insight Hereditary Tumors databases. The variant was only identified in ClinVar (classified as likely benign by GeneDx). The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Leu160= 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. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) 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.