Submissions for variant NM_000455.5(STK11):c.1038C>T (p.Gly346=)

gnomAD frequency: 0.00011  dbSNP: rs767565606

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163139	SCV000213655	likely benign	Hereditary cancer-predisposing syndrome	2015-02-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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	RCV000198223	SCV000254536	benign	Peutz-Jeghers syndrome	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000427198	SCV000519100	likely benign	not specified	2017-08-15	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001800476	SCV000602204	likely benign	not provided	2022-10-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163139	SCV000691463	likely benign	Hereditary cancer-predisposing syndrome	2016-04-27	criteria provided, single submitter	clinical testing
Counsyl	RCV000198223	SCV000784886	likely benign	Peutz-Jeghers syndrome	2017-01-27	criteria provided, single submitter	clinical testing
Mendelics	RCV003492670	SCV000839424	likely benign	Hereditary cancer	2024-01-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000427198	SCV000920281	likely benign	not specified	2021-07-26	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798570	SCV002042759	uncertain significance	Breast and/or ovarian cancer	2020-03-25	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000198223	SCV002057305	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000198223	SCV004017908	benign	Peutz-Jeghers syndrome	2023-04-12	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.
PreventionGenetics, part of Exact Sciences	RCV003407603	SCV004112158	uncertain significance	STK11-related condition	2023-12-05	criteria provided, single submitter	clinical testing	The STK11 c.1038C>T variant is not predicted to result in an amino acid change (p.=). Based on available splicing prediction programs (Alamut Visual Plus v1.6.1) this variant is predicted to create a cryptic splice donor site; however, to date this prediction has not been proven by functional studies. This variant has been observed once in a cohort of individuals who underwent genetic counseling for risk assessment of breast, ovarian, and endometrial cancer and reported as benign/likely benign (Table 1, Carvalho et al. 2023. PubMed ID: 36977404). It is observed at an allele frequency of up to ~0.0033% in a large population database and has conflicting interpretations of benign, likely benign and uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/184026/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.