Submissions for variant NM_000455.5(STK11):c.449T>C (p.Val150Ala)

gnomAD frequency: 0.00001  dbSNP: rs587781802

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000130068	SCV000184895	likely benign	Hereditary cancer-predisposing syndrome	2022-12-27	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000199606	SCV000254551	benign	Peutz-Jeghers syndrome	2024-11-17	criteria provided, single submitter	clinical testing
Counsyl	RCV000199606	SCV000489718	uncertain significance	Peutz-Jeghers syndrome	2016-11-11	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000130068	SCV000686649	uncertain significance	Hereditary cancer-predisposing syndrome	2023-01-25	criteria provided, single submitter	clinical testing	This missense variant replaces valine with alanine at codon 150 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 hereditary cancer in the literature. This variant has been identified in 3/212626 chromosomes 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	RCV001557521	SCV001779294	uncertain significance	not provided	2024-06-03	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; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15863673)
Genome-Nilou Lab	RCV000199606	SCV002057796	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000199606	SCV004017999	uncertain significance	Peutz-Jeghers syndrome	2023-04-14	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
PreventionGenetics, part of Exact Sciences	RCV003415947	SCV004107218	uncertain significance	STK11-related disorder	2023-02-21	criteria provided, single submitter	clinical testing	The STK11 c.449T>C variant is predicted to result in the amino acid substitution p.Val150Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0032% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-1219397-T-C) and is interpreted as uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/141508/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000582047	SCV004241781	uncertain significance	not specified	2023-12-31	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000199606	SCV004816361	uncertain significance	Peutz-Jeghers syndrome	2024-08-06	criteria provided, single submitter	clinical testing	This missense variant replaces valine with alanine at codon 150 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 hereditary cancer in the literature. This variant has been identified in 3/212626 chromosomes 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000582047	SCV000692044	uncertain significance	not specified		no assertion criteria provided	clinical testing