ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1063G>A (p.Asp355Asn) (rs769403473)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000505996 SCV000920276 uncertain significance not specified 2018-03-12 criteria provided, single submitter clinical testing Variant summary: STK11 c.1063G>A (p.Asp355Asn) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant of interest was observed with an allele frequency of 4.1e-06 in 2472790 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.1063G>A has been reported in the literature in individuals being tested on commercial cancer gene panels. These report(s) do not provide unequivocal conclusions about association of the variant with Peutz-Jeghers Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as "uncertain significance." Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000815148 SCV000955594 uncertain significance Peutz-Jeghers syndrome 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 355 of the STK11 protein (p.Asp355Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. 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: 439299). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000505996 SCV000602205 uncertain significance not specified 2016-10-13 criteria provided, single submitter clinical testing

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