ClinVar Miner

Submissions for variant NM_005359.5(SMAD4):c.634G>A (p.Ala212Thr) (rs863224732)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000198746 SCV000254842 uncertain significance Juvenile polyposis syndrome 2017-03-15 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 212 of the SMAD4 protein (p.Ala212Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SMAD4-related disease. ClinVar contains an entry for this variant (Variation ID: 216603). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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