ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1252T>A (p.Cys418Ser) (rs730881991)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000161014 SCV000211728 uncertain significance not provided 2014-07-22 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1252T>A at the cDNA level, p.Cys418Ser (C418S) at the protein level, and results in the change of a Cysteine to a Serine (TGC>AGC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 Cys418Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Cysteine and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. STK11 Cys418Ser occurs at a position that is moderately conserved through mammals and is located in domain that undergoes S-palmitoylation (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether STK11 Cys418Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000564627 SCV000664362 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000699445 SCV000828157 uncertain significance Peutz-Jeghers syndrome 2018-04-19 criteria provided, single submitter clinical testing This sequence change replaces cysteine with serine at codon 418 of the STK11 protein (p.Cys418Ser). The cysteine residue is moderately conserved and there is a moderate physicochemical difference between cysteine and serine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 182919). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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