Submissions for variant NM_000455.5(STK11):c.900C>T (p.Ile300=)

gnomAD frequency: 0.00011  dbSNP: rs546089394

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000213025	SCV000211689	benign	not specified	2014-02-07	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	RCV000160979	SCV000213604	likely benign	Hereditary cancer-predisposing syndrome	2016-08-05	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001085913	SCV000284880	likely benign	Peutz-Jeghers syndrome	2024-01-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000160979	SCV000691558	likely benign	Hereditary cancer-predisposing syndrome	2017-08-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000213025	SCV000696731	benign	not specified	2019-03-22	criteria provided, single submitter	clinical testing	Variant summary: STK11 c.900C>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 0.00013 in 30928 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.900C>T in individuals affected with Peutz-Jeghers Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with another pathogenic variant has been reported (PMS2 c.2186_2187delTC, p.Leu729fsX6) in our internal database. In addition, this variant was found in 3/2559 African American women who are older than age of 70 years and cancer free (FLOSSIES database), providing supporting evidence for a benign role. Three 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000586525	SCV001134852	benign	not provided	2019-06-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001085913	SCV002057445	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000160979	SCV002526957	benign	Hereditary cancer-predisposing syndrome	2021-06-15	criteria provided, single submitter	curation
All of Us Research Program, National Institutes of Health	RCV001085913	SCV004818933	likely benign	Peutz-Jeghers syndrome	2023-12-13	criteria provided, single submitter	clinical testing