ClinVar Miner

Submissions for variant NM_005359.5(SMAD4):c.127T>G (p.Leu43Val) (rs863224731)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000199820 SCV000254840 uncertain significance Juvenile polyposis syndrome 2015-04-08 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 43 of the SMAD4 protein (p.Leu43Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant has not been reported in affected patients, and is not present in population databases. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). However, experimental studies have shown that this missense change disrupts the DNA binding and transcriptional transactivation activities of the SMAD4 protein (PMID: 14647410). In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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