ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.856G>A (p.Asp286Asn)

gnomAD frequency: 0.00007  dbSNP: rs759918873
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001755445 SCV002005662 uncertain significance not provided 2021-01-14 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp RCV001885083 SCV002147835 uncertain significance Aortic valve disease 2 2023-11-14 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 286 of the SMAD6 protein (p.Asp286Asn). This variant is present in population databases (rs759918873, gnomAD 0.004%). 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: 1315783). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SMAD6 protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV003163895 SCV003888102 uncertain significance Inborn genetic diseases 2023-02-28 criteria provided, single submitter clinical testing The c.856G>A (p.D286N) alteration is located in exon 2 (coding exon 2) of the SMAD6 gene. This alteration results from a G to A substitution at nucleotide position 856, causing the aspartic acid (D) at amino acid position 286 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.