Submissions for variant NM_000455.5(STK11):c.945G>A (p.Pro315=)

gnomAD frequency: 0.00060  dbSNP: rs376329042

Total submissions: 25

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000990133	SCV000166363	benign	Peutz-Jeghers syndrome	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000213027	SCV000171893	benign	not specified	2013-11-01	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	RCV000128301	SCV000213093	likely benign	Hereditary cancer-predisposing syndrome	2014-06-16	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.
Color Diagnostics, LLC DBA Color Health	RCV000128301	SCV000686707	likely benign	Hereditary cancer-predisposing syndrome	2015-06-09	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756723	SCV000884615	likely benign	not provided	2021-05-06	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000213027	SCV000888650	benign	not specified	2021-07-21	criteria provided, single submitter	clinical testing
Mendelics	RCV000990133	SCV001140945	likely benign	Peutz-Jeghers syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000990133	SCV001285140	benign	Peutz-Jeghers syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000756723	SCV001747895	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	STK11: BP4, BP7
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798403	SCV002042775	likely benign	Breast and/or ovarian cancer	2023-06-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000990133	SCV002057449	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000213027	SCV002065829	likely benign	not specified	2019-09-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000128301	SCV002526964	benign	Hereditary cancer-predisposing syndrome	2020-10-20	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000213027	SCV002552029	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000128301	SCV002819204	benign	Hereditary cancer-predisposing syndrome	2022-10-04	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000990133	SCV004015572	benign	Peutz-Jeghers syndrome	2023-07-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003935174	SCV004747372	benign	STK11-related disorder	2019-05-14	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
All of Us Research Program, National Institutes of Health	RCV000990133	SCV004818942	likely benign	Peutz-Jeghers syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000213027	SCV000692053	likely benign	not specified		no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000128301	SCV000788221	likely benign	Hereditary cancer-predisposing syndrome	2017-12-01	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357889	SCV001553484	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The STK11 p.Pro315= variant was identified in 2 of 144 proband chromosomes (frequency: 0.01) from Spanish and Australian individuals or families with Lynch syndrome or PJS (Peutz–Jeghers syndrome (Vargas-Parra_2017_28577310, Scott_2002_12372054 ). The variant was also identified in dbSNP (ID: rs376329042) “With Likely benign allele”, ClinVar (classified benign by Invitae, GeneDx, and Quest Diagnostics Nichols Institute San Juan Capistrano, and likely benign by Ambry Genetics), Clinvitae (3x), Cosmic (1x in a carcinoma of the large intestine), Zhejiang Colon Cancer Database (8x), and in control databases in 150 of 218304 chromosomes at a frequency of 0.0007 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 3 of 19118 chromosomes (freq: 0.0002), Other in 3 of 5448 chromosomes (freq: 0.0006), Latino in 10 of 28572 chromosomes (freq: 0.0004), European Non-Finnish in 66 of 95490 chromosomes (freq: 0.0007), Ashkenazi Jewish in 48 of 8990 chromosomes (freq: 0.005), European Finnish in 2 of 20554 chromosomes (freq: 0.0001), and South Asian in 18 of 25328 chromosomes (freq: 0.0007) while not observed in the East Asian population. The variant was not identified in MutDB, LOVD 3.0, and Insight Hereditary Tumors Database The p.Pro315= 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000756723	SCV001741439	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000756723	SCV001808518	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000756723	SCV001917834	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000756723	SCV002035730	likely benign	not provided		no assertion criteria provided	clinical testing