Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000818824 | SCV000959458 | uncertain significance | Aortic valve disease 2 | 2023-06-20 | criteria provided, single submitter | clinical testing | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 661416). This variant has not been reported in the literature in individuals affected with SMAD6-related conditions. This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 28 of the SMAD6 protein (p.Gly28Ser). |
| Ambry Genetics | RCV002535486 | SCV003592522 | uncertain significance | Inborn genetic diseases | 2021-10-26 | criteria provided, single submitter | clinical testing | The c.82G>A (p.G28S) 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 82, causing the glycine (G) at amino acid position 28 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |