Submissions for variant NM_000455.5(STK11):c.1253G>C (p.Cys418Ser)

dbSNP: rs878853986

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000231843	SCV000284854	likely benign	Peutz-Jeghers syndrome	2024-12-15	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001184074	SCV001349966	uncertain significance	Hereditary cancer-predisposing syndrome	2023-03-01	criteria provided, single submitter	clinical testing	This missense variant replaces cysteine with serine at codon 418 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 reported for this variant. This variant has not been reported in individuals affected with STK11-related disorders 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.
GeneDx	RCV001753688	SCV001997045	uncertain significance	not provided	2024-07-23	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in a breast cancer study, but it is not clear if the variant was identified in case(s) or control(s) (PMID: 31871109); This variant is associated with the following publications: (PMID: 28900777, 31871109)
Genome-Nilou Lab	RCV000231843	SCV002057994	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001184074	SCV002676403	likely benign	Hereditary cancer-predisposing syndrome	2024-10-25	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.
Revvity Omics, Revvity	RCV000231843	SCV003818111	uncertain significance	Peutz-Jeghers syndrome	2022-11-24	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492000	SCV004239716	uncertain significance	Breast and/or ovarian cancer	2022-09-26	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000231843	SCV004819023	uncertain significance	Peutz-Jeghers syndrome	2024-05-30	criteria provided, single submitter	clinical testing	This missense variant replaces cysteine with serine at codon 418 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 reported for this variant. This variant has not been reported in individuals affected with STK11-related disorders 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.