Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001334425 | SCV001527271 | uncertain significance | Aortic valve disease 2 | 2018-11-03 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Ambry Genetics | RCV002438765 | SCV002750689 | uncertain significance | Inborn genetic diseases | 2024-03-19 | criteria provided, single submitter | clinical testing | The c.298G>A (p.A100T) alteration is located in exon 1 (coding exon 1) of the SMAD6 gene. This alteration results from a G to A substitution at nucleotide position 298, causing the alanine (A) at amino acid position 100 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001334425 | SCV004304333 | uncertain significance | Aortic valve disease 2 | 2023-11-25 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 100 of the SMAD6 protein (p.Ala100Thr). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 1032339). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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. |