ClinVar Miner

Submissions for variant NM_005359.6(SMAD4):c.404G>T (p.Arg135Leu)

dbSNP: rs2144406204
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001892167 SCV002154376 uncertain significance Juvenile polyposis syndrome 2021-05-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 135 of the SMAD4 protein (p.Arg135Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SMAD4-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SMAD4 protein function. 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.

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