ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.1465G>A (p.Glu489Lys)

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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 RCV003648089 SCV004375329 uncertain significance Aortic valve disease 2 2023-10-09 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 489 of the SMAD6 protein (p.Glu489Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with craniosynostosis (PMID: 32499606). 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 SMAD6 protein function. Experimental studies have shown that this missense change affects SMAD6 function (PMID: 32499606). 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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