Submissions for variant NM_000455.5(STK11):c.787T>C (p.Leu263=)

gnomAD frequency: 0.00010  dbSNP: rs372378119

Total submissions: 23

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000213018	SCV000171889	benign	not specified	2014-04-24	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	RCV000128297	SCV000213594	likely benign	Hereditary cancer-predisposing syndrome	2014-07-12	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	RCV000200266	SCV000253263	benign	Peutz-Jeghers syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000200266	SCV000487850	likely benign	Peutz-Jeghers syndrome	2015-11-20	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000128297	SCV000537494	likely benign	Hereditary cancer-predisposing syndrome	2015-08-10	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001528533	SCV000602236	benign	not provided	2021-03-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001528533	SCV001747894	likely benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	STK11: BP4, BP7
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798431	SCV002042774	likely benign	Breast and/or ovarian cancer	2022-09-21	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000200266	SCV002057435	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000128297	SCV002526937	benign	Hereditary cancer-predisposing syndrome	2020-10-30	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000200266	SCV004015576	benign	Peutz-Jeghers syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000200266	SCV004017996	benign	Peutz-Jeghers syndrome	2023-04-14	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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000213018	SCV004026952	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000128297	SCV004228048	likely benign	Hereditary cancer-predisposing syndrome	2023-08-04	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000200266	SCV004818907	likely benign	Peutz-Jeghers syndrome	2024-02-05	criteria provided, single submitter	clinical testing
True Health Diagnostics	RCV000128297	SCV000788219	likely benign	Hereditary cancer-predisposing syndrome	2017-08-11	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354164	SCV001548708	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The STK11 p.Leu263= variant was not identified in the literature. The variant was identified in dbSNP (rs372378119) as “with other allele”, ClinVar (classified as likely benign by Color, Ambry Genetics, Counsyl, Quest Diagnostics and True Health Diagnostics and benign by Invitae and GeneDx) and LOVD 3.0 (observed 3x). The variant was identified in control databases in 52 of 278,592 chromosomes at a frequency of 0.000187 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Ashkenazi Jewish in 7 of 10,250 chromosomes (freq: 0.0007), European in 36 of 127,104 chromosomes (freq: 0.0003), Other in 2 of 7086 chromosomes (freq: 0.0003), Finnish in 5 of 24,994 chromosomes (freq: 0.0002), South Asian in 2 of 30,470 chromosomes (freq: 0.00007), while the variant was not observed in the African, Latino and East Asian populations. The p.Leu263= 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528533	SCV001740402	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001528533	SCV001919901	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001528533	SCV001959233	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001528533	SCV002033857	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001528533	SCV002035158	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003945142	SCV004775058	likely benign	STK11-related disorder	2019-07-09	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).