Submissions for variant NM_000455.5(STK11):c.765C>T (p.Phe255=)

gnomAD frequency: 0.00001  dbSNP: rs769912677

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163717	SCV000214291	likely benign	Hereditary cancer-predisposing syndrome	2014-12-30	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	RCV000465289	SCV000554131	likely benign	Peutz-Jeghers syndrome	2024-01-27	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163717	SCV000686688	likely benign	Hereditary cancer-predisposing syndrome	2015-12-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001538194	SCV001755808	benign	not provided	2015-09-24	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000465289	SCV002057434	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163717	SCV002526934	likely benign	Hereditary cancer-predisposing syndrome	2021-11-26	criteria provided, single submitter	curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002281977	SCV002570607	likely benign	not specified	2022-07-07	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002281977	SCV002761026	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003895112	SCV004712380	likely benign	STK11-related disorder	2022-05-26	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	RCV000465289	SCV004818904	likely benign	Peutz-Jeghers syndrome	2023-11-30	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357154	SCV001552525	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The STK11 p.Phe255Phe variant was not identified in the literature nor was it identified in the COSMIC, MutDB, LOVD 3.0, Zhejiang Colon Cancer Database, or Insight Hereditary Tumors Database. The variant was identified in dbSBP (ID: rs769912677) as “With Likely benign allele”, ClinVar (2x likely benign: Ambry Genetics, Invitae), Clinvitae (2x likely benign: Invitae, ClinVar), databases. The variant was identified in control databases in 4 of 276208 chromosomes (3x European non-Finnish, 1x European Finnish) at a frequency of 0.00001 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.Phe255Phe 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 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.