ClinVar Miner

Submissions for variant NM_005359.5(SMAD4):c.910G>A (p.Val304Ile) (rs375185293)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000203937 SCV000259398 uncertain significance Juvenile polyposis syndrome 2018-09-02 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 304 of the SMAD4 protein (p.Val304Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs375185293, ExAC 0.002%). This variant has not been reported in the literature in individuals with SMAD4-related disease. ClinVar contains an entry for this variant (Variation ID: 219504). 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.
Counsyl RCV000203937 SCV000489309 uncertain significance Juvenile polyposis syndrome 2016-09-15 criteria provided, single submitter clinical testing

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