ClinVar Miner

Submissions for variant NM_000455.5(STK11):c.719C>G (p.Ser240Trp)

dbSNP: rs730881976
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000160995 SCV000278089 likely pathogenic Hereditary cancer-predisposing syndrome 2020-09-18 criteria provided, single submitter clinical testing The p.S240W variant (also known as c.719C>G), located in coding exon 5 of the STK11 gene, results from a C to G substitution at nucleotide position 719. The serine at codon 240 is replaced by tryptophan, an amino acid with highly dissimilar properties. This alteration has been reported in individuals with clinical features of Peutz-Jeghers syndrome (Ngeow J et al. Gastroenterology 2013 Jun; 144(7):1402-9, 1409.e1-5; Zhang Z et al. World J. Gastroenterol. 2020 Apr;26(16):1926-1937; Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000763422 SCV000894180 likely pathogenic Carcinoma of pancreas; Peutz-Jeghers syndrome; Malignant tumor of testis 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001041130 SCV001204728 likely pathogenic Peutz-Jeghers syndrome 2023-03-23 criteria provided, single submitter clinical testing This missense change has been observed in individuals with Peutz-Jeghers syndrome (PMID: 23399955; Invitae). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt STK11 protein function. ClinVar contains an entry for this variant (Variation ID: 182902). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 240 of the STK11 protein (p.Ser240Trp).
Genome-Nilou Lab RCV001041130 SCV002057275 likely pathogenic Peutz-Jeghers syndrome 2021-07-15 criteria provided, single submitter clinical testing

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