ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.715G>A (p.Val239Met)

gnomAD frequency: 0.00004  dbSNP: rs768794005
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001367884 SCV001564254 uncertain significance Aortic valve disease 2 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 239 of the SMAD6 protein (p.Val239Met). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of SMAD6-related conditions (PMID: 28659821, 32499606). ClinVar contains an entry for this variant (Variation ID: 1058716). 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 not expected to disrupt SMAD6 protein function with a negative predictive value of 80%. 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.
Breakthrough Genomics, Breakthrough Genomics RCV004692653 SCV005193895 uncertain significance not provided criteria provided, single submitter not provided

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