ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.970C>T (p.Pro324Ser) (rs549474196)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000775661 SCV000910055 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-17 criteria provided, single submitter clinical testing
GeneDx RCV000115607 SCV000149516 uncertain significance not provided 2014-03-04 criteria provided, single submitter clinical testing This variant is denoted STK11 c.970C>T at the cDNA level, p.Pro324Ser (P324S) at the protein level, and results in the change of a Proline to a Serine (CCG>TCG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign; however, a different missense variant at the same position, STK11 Pro324Leu has been reported in the literature also as a variant of uncertain significance. STK11 Pro324Ser 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 Proline and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution and is likely to affect protein integrity. STK11 Pro324Ser occurs at a position that is conserved across species and is not located in a known functional domain per UniProt. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether STK11 Pro324Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000467660 SCV000541170 uncertain significance Peutz-Jeghers syndrome 2018-01-24 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 324 of the STK11 protein (p.Pro324Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 127711). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Mendelics RCV000467660 SCV000839423 uncertain significance Peutz-Jeghers syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000115607 SCV000888653 uncertain significance not provided 2018-01-05 criteria provided, single submitter clinical testing

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