Submissions for variant NM_000455.5(STK11):c.678C>T (p.Asn226=)

gnomAD frequency: 0.00005  dbSNP: rs748832988

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163416	SCV000213959	likely benign	Hereditary cancer-predisposing syndrome	2015-11-18	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.
Counsyl	RCV000411450	SCV000488921	likely benign	Peutz-Jeghers syndrome	2016-07-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001704165	SCV000515584	likely benign	not provided	2019-01-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000411450	SCV000554133	likely benign	Peutz-Jeghers syndrome	2025-01-13	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163416	SCV000686674	likely benign	Hereditary cancer-predisposing syndrome	2016-07-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002228570	SCV002511507	likely benign	not specified	2022-04-28	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002228570	SCV002552020	likely benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000411450	SCV004017930	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.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357469	SCV001552950	likely benign	Bile duct cancer		no assertion criteria provided	clinical testing	The STK11 p.Asn226= variant was not identified in the literature nor was it identified in the following databases: Cosmic, MutDB, LOVD 3.0, Zhejiang Colon Cancer Database, or Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs748832988) “With Likely benign allele”, ClinVar (classified likely benign by Ambry Genetics, Counsyl, GeneDx and Invitae), Clinvitae (3x), and in control databases in 10 of 271382 chromosomes at a frequency of 0.00004 (Genome Aggregation Database Feb 27, 2017). Observation by population include European Non-Finnish in 9 of 122798 chromosomes (freq: 0.00007) and East Asian in 1 of 18748 chromosomes (freq: 0.00005); it was not observed in the African, Other, Latino, Ashkenazi Jewish, European Finnish, and South Asian populations. The p.Asn226= 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.