Submissions for variant NM_000455.5(STK11):c.1283C>T (p.Ser428Leu)

gnomAD frequency: 0.00001  dbSNP: rs587781537

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000218637	SCV000279226	uncertain significance	not provided	2019-09-18	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18321849, 18854309)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000476552	SCV000541128	benign	Peutz-Jeghers syndrome	2024-10-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000567419	SCV000672309	benign	Hereditary cancer-predisposing syndrome	2024-01-17	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Color Diagnostics, LLC DBA Color Health	RCV000567419	SCV000686616	uncertain significance	Hereditary cancer-predisposing syndrome	2023-02-28	criteria provided, single submitter	clinical testing	This missense variant replaces serine with leucine at codon 428 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Genome-Nilou Lab	RCV000476552	SCV002058014	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150130	SCV003838206	uncertain significance	Breast and/or ovarian cancer	2021-08-06	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000476552	SCV004819036	uncertain significance	Peutz-Jeghers syndrome	2024-05-30	criteria provided, single submitter	clinical testing	This missense variant replaces serine with leucine at codon 428 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.