ClinVar Miner

Submissions for variant NM_005359.6(SMAD4):c.1186G>A (p.Asp396Asn)

dbSNP: rs2144452017
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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 RCV001872297 SCV002121379 uncertain significance Juvenile polyposis syndrome 2021-06-06 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 396 of the SMAD4 protein (p.Asp396Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. 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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