Submissions for variant NM_000455.5(STK11):c.71C>T (p.Thr24Met)

gnomAD frequency: 0.00001  dbSNP: rs770503805

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000472539	SCV000541139	likely benign	Peutz-Jeghers syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000568581	SCV000672318	likely benign	Hereditary cancer-predisposing syndrome	2023-04-07	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.
Color Diagnostics, LLC DBA Color Health	RCV000568581	SCV000686676	uncertain significance	Hereditary cancer-predisposing syndrome	2023-01-18	criteria provided, single submitter	clinical testing	This missense variant replaces threonine with methionine at codon 24 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 been reported in individuals affected with leukemia (PMID: 26580448) and prostate cancer (PMID: 29368341). This variant has been identified in 2/245242 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.
Genome-Nilou Lab	RCV000472539	SCV002057731	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000568581	SCV002531724	uncertain significance	Hereditary cancer-predisposing syndrome	2021-09-16	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477937	SCV004221288	uncertain significance	not provided	2023-08-18	criteria provided, single submitter	clinical testing	In the published literature, this variant has been reported in individuals with prostate cancer (PMID: 29368341 (2018)) and acute myeloid leukemia (PMID: 26580448 (2015)). In a breast cancer association study, this variant was reported both in healthy individuals and those with breast cancer (PMID: 33471991 (2021), see also LOVD (https://databases.lovd.nl/shared/variants/STK11)). The frequency of this variant in the general population, 0.0000082 (2/245242 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 predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
All of Us Research Program, National Institutes of Health	RCV000472539	SCV004816308	uncertain significance	Peutz-Jeghers syndrome	2024-01-11	criteria provided, single submitter	clinical testing	This missense variant replaces threonine with methionine at codon 24 of the STK11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with leukemia (PMID: 26580448) and prostate cancer (PMID: 29368341) This variant has been identified in 2/245242 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.
Baylor Genetics	RCV004567933	SCV005052870	uncertain significance	Melanoma, cutaneous malignant, susceptibility to, 1	2024-03-17	criteria provided, single submitter	clinical testing
GeneDx	RCV003477937	SCV005078163	uncertain significance	not provided	2023-10-09	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; Reported in individuals with colorectal or acute megakaryoblastic leukemia, as well as both cases and controls in a breast cancer study (Zhang et al., 2015; Hampel et al., 2018; Dorling et al., 2021); This variant is associated with the following publications: (PMID: 26580448, 29368341, 33471991, 29596542)