ClinVar Miner

Submissions for variant NM_000455.5(STK11):c.941C>T (p.Pro314Leu)

gnomAD frequency: 0.00001  dbSNP: rs1064795752
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483299 SCV000571863 uncertain significance not provided 2018-12-03 criteria provided, single submitter clinical testing This variant is denoted STK11 c.941C>T at the cDNA level, p.Pro314Leu (P314L) at the protein level, and results in the change of a Proline to a Leucine (CCT>CTT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. STK11 Pro314Leu was not observed in large population cohorts (Lek 2016). This variant is located in the c-terminal domain (Daniell 2017). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether STK11 Pro314Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV001019328 SCV001180672 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-27 criteria provided, single submitter clinical testing The p.P314L variant (also known as c.941C>T), located in coding exon 8 of the STK11 gene, results from a C to T substitution at nucleotide position 941. The proline at codon 314 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001219458 SCV001391398 uncertain significance Peutz-Jeghers syndrome 2023-06-23 criteria provided, single submitter clinical testing 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. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 314 of the STK11 protein (p.Pro314Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 422396). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on STK11 protein function.
Genome-Nilou Lab RCV001219458 SCV002057878 uncertain significance Peutz-Jeghers syndrome 2021-07-15 criteria provided, single submitter clinical testing

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