ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.278T>C (p.Met93Thr)

gnomAD frequency: 0.00006  dbSNP: rs985309653
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001316828 SCV001507466 uncertain significance Aortic valve disease 2 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 93 of the SMAD6 protein (p.Met93Thr). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SMAD6-related conditions. ClinVar contains an entry for this variant (Variation ID: 405514). 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. 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.
GeneDx RCV001753870 SCV002006184 uncertain significance not provided 2020-06-29 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV003278808 SCV003984453 uncertain significance Inborn genetic diseases 2023-07-31 criteria provided, single submitter clinical testing The p.M93T variant (also known as c.278T>C), located in coding exon 1 of the SMAD6 gene, results from a T to C substitution at nucleotide position 278. The methionine at codon 93 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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