ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1015C>G (p.Pro339Ala) (rs769644352)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165885 SCV000216636 uncertain significance Hereditary cancer-predisposing syndrome 2014-09-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000781886 SCV000920269 uncertain significance not specified 2017-11-09 criteria provided, single submitter clinical testing Variant summary: The STK11 c.1015C>G (p.Pro339Ala) variant involves the alteration of a conserved nucleotide and 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). However, these predictions have yet to be functionally assessed. This variant is absent in 237456 control chromosomes (gnomAD). In addition, a clinical diagnostic laboratory classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.
Invitae RCV000534169 SCV000629054 uncertain significance Peutz-Jeghers syndrome 2018-08-03 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 339 of the STK11 protein (p.Pro339Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. 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: 186311). 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.

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