ClinVar Miner

Submissions for variant NM_000455.5(STK11):c.997C>T (p.Arg333Cys)

dbSNP: rs746564972
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001181037 SCV001346097 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-04 criteria provided, single submitter clinical testing This missense variant replaces arginine with cysteine at codon 333 of the STK11 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 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.
Invitae RCV001202795 SCV001373922 uncertain significance Peutz-Jeghers syndrome 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 333 of the STK11 protein (p.Arg333Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs746564972, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with STK11-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab RCV001202795 SCV002057896 uncertain significance Peutz-Jeghers syndrome 2021-07-15 criteria provided, single submitter clinical testing
GeneDx RCV002254954 SCV002526170 uncertain significance not provided 2022-06-06 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28900777)
Ambry Genetics RCV001181037 SCV002695440 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-13 criteria provided, single submitter clinical testing The p.R333C variant (also known as c.997C>T), located in coding exon 8 of the STK11 gene, results from a C to T substitution at nucleotide position 997. The arginine at codon 333 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002465838 SCV002761028 uncertain significance not specified 2023-08-15 criteria provided, single submitter clinical testing

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