ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.1348C>A (p.Pro450Thr)

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 RCV002035818 SCV002296891 uncertain significance Aortic valve disease 2 2021-11-27 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with SMAD6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 450 of the SMAD6 protein (p.Pro450Thr).
PreventionGenetics, part of Exact Sciences RCV003402048 SCV004105542 uncertain significance SMAD6-related disorder 2023-07-16 criteria provided, single submitter clinical testing The SMAD6 c.1348C>A variant is predicted to result in the amino acid substitution p.Pro450Thr. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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