ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1229C>T (p.Ala410Val) (rs372329880)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000213038 SCV000149506 uncertain significance not provided 2019-01-04 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1229C>T at the cDNA level, p.Ala410Val (A410V) at the protein level, and results in the change of an Alanine to a Valine (GCC>GTC). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. STK11 Ala410Val 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 that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether STK11 Ala410Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000115597 SCV000185482 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000200053 SCV000254545 uncertain significance Peutz-Jeghers syndrome 2018-08-28 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 410 of the STK11 protein (p.Ala410Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs372329880, ExAC 0.08%). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 127701). 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.
Color RCV000115597 SCV000691481 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-10 criteria provided, single submitter clinical testing

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