Submissions for variant NM_000455.5(STK11):c.882G>A (p.Pro294=)

gnomAD frequency: 0.00001  dbSNP: rs587781178

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000213023	SCV000171891	benign	not specified	2013-12-24	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	RCV000128299	SCV000214189	likely benign	Hereditary cancer-predisposing syndrome	2014-10-30	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.
Invitae	RCV000473797	SCV000554115	likely benign	Peutz-Jeghers syndrome	2024-01-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000128299	SCV000686700	likely benign	Hereditary cancer-predisposing syndrome	2017-03-08	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000213023	SCV002046997	likely benign	not specified	2021-04-23	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000473797	SCV002057443	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000128299	SCV002526955	likely benign	Hereditary cancer-predisposing syndrome	2021-08-19	criteria provided, single submitter	curation
PreventionGenetics, part of Exact Sciences	RCV003905222	SCV004721838	likely benign	STK11-related disorder	2024-03-02	criteria provided, single submitter	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).
All of Us Research Program, National Institutes of Health	RCV000473797	SCV004818931	likely benign	Peutz-Jeghers syndrome	2023-08-28	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357918	SCV001553519	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The STK11 p.Pro294= variant was not identified in the literature nor was it identified in the MutDB, LOVD 3.0, Zhejiang Colon Cancer Database, Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs587781178) “With Likely benign allele,” ClinVar (as benign by GeneDx and likely benign by Ambry Genetics and Invitae), Clinvitae, and Cosmic databases. The variant was identified in control databases in 4 of 169630 chromosomes at a frequency of 0.000024 increasing the likelihood that this may be a low frequency benign variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017). The p.Pro294= 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.