ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.1348C>T (p.Pro450Ser)

gnomAD frequency: 0.00002  dbSNP: rs369864879
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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 RCV001294583 SCV001483464 uncertain significance Aortic valve disease 2 2022-01-12 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 998694). This variant has not been reported in the literature in individuals affected with SMAD6-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.005%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 450 of the SMAD6 protein (p.Pro450Ser).
Ambry Genetics RCV002379984 SCV002694878 uncertain significance Inborn genetic diseases 2021-11-19 criteria provided, single submitter clinical testing The p.P450S variant (also known as c.1348C>T), located in coding exon 4 of the SMAD6 gene, results from a C to T substitution at nucleotide position 1348. The proline at codon 450 is replaced by serine, 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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