ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.328C>T (p.Pro110Ser)

gnomAD frequency: 0.00023  dbSNP: rs773431944
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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 RCV001338853 SCV001532555 uncertain significance Aortic valve disease 2 2020-10-01 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 serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SMAD6-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces proline with serine at codon 110 of the SMAD6 protein (p.Pro110Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine.
Ambry Genetics RCV003294329 SCV004007150 uncertain significance Inborn genetic diseases 2023-04-18 criteria provided, single submitter clinical testing The p.P110S variant (also known as c.328C>T), located in coding exon 1 of the SMAD6 gene, results from a C to T substitution at nucleotide position 328. The proline at codon 110 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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