Submissions for variant NM_000455.5(STK11):c.1284G>C (p.Ser428=)

dbSNP: rs369097329

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163891	SCV000214482	likely benign	Hereditary cancer-predisposing syndrome	2016-04-28	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	RCV000197355	SCV000253247	likely benign	Peutz-Jeghers syndrome	2024-01-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163891	SCV000686618	likely benign	Hereditary cancer-predisposing syndrome	2016-09-02	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000197355	SCV004819038	likely benign	Peutz-Jeghers syndrome	2023-10-06	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354357	SCV001548954	likely benign	Malignant neoplasm of brain		no assertion criteria provided	clinical testing	The STK11 p.Ser428= variant was not identified in the literature. The variant was identified in dbSNP (ID: rs369097329) as “With Likely benign allele”, ClinVar (3x as likely benign by Ambry Genetics, Invitae, Color) and LOVD 3.0 (1x as benign). The variant was identified in control databases in 5 of 135876 chromosomes at a frequency of 0.000037 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: East Asian in 5 of 9960 chromosomes (freq: 0.0005), but not in the African, Other, Latino, European Non-Finnish, Ashkenazi Jewish, European Finnish or South Asian populations. The p.Ser428= 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) 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.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356667	SCV001551899	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The STK11 p.Ser428= variant was not identified in the literature. The variant was identified in dbSNP (ID: rs369097329) as “With Likely benign allele”, ClinVar (3x as likely benign by Ambry Genetics, Invitae, Color) and LOVD 3.0 (1x as benign). The variant was identified in control databases in 5 of 135876 chromosomes at a frequency of 0.000037 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: East Asian in 5 of 9960 chromosomes (freq: 0.0005), but not in the African, Other, Latino, European Non-Finnish, Ashkenazi Jewish, European Finnish or South Asian populations. The p.Ser428= 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) 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.