Submissions for variant NM_000455.5(STK11):c.1276C>G (p.Arg426Gly)

dbSNP: rs587782687

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000132118	SCV000187186	likely benign	Hereditary cancer-predisposing syndrome	2023-03-10	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	RCV000410170	SCV000488871	uncertain significance	Peutz-Jeghers syndrome	2016-07-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000485540	SCV000570750	uncertain significance	not provided	2024-01-09	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with malignant pleural mesothelioma (PMID: 26928227); This variant is associated with the following publications: (PMID: 28900777, 23399955, 26928227)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000410170	SCV000629091	benign	Peutz-Jeghers syndrome	2024-07-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000132118	SCV001348640	uncertain significance	Hereditary cancer-predisposing syndrome	2023-11-02	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glycine at codon 426 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.
Genome-Nilou Lab	RCV000410170	SCV002058009	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000410170	SCV004018011	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.
Baylor Genetics	RCV003462033	SCV004205574	uncertain significance	Melanoma, cutaneous malignant, susceptibility to, 1	2023-07-16	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000410170	SCV004819029	uncertain significance	Peutz-Jeghers syndrome	2023-11-20	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glycine at codon 426 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000485540	SCV005624856	uncertain significance	not provided	2024-09-28	criteria provided, single submitter	clinical testing	The STK11 c.1276C>G (p.Arg426Gly) variant has been reported in the published literature in an individual with malignant pleural mesothelioma (PMID: 26928227 (2016)). The frequency of this variant in the general population, 0.0000066 (1/152220 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant.