ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.482C>T (p.Ala161Val)

gnomAD frequency: 0.00012  dbSNP: rs748622672
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231880 SCV000288924 uncertain significance Aortic valve disease 2 2023-11-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 161 of the SMAD6 protein (p.Ala161Val). This variant is present in population databases (rs748622672, gnomAD 0.03%). 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: 240179). 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 RCV002338737 SCV002635085 likely benign Inborn genetic diseases 2022-02-11 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003401179 SCV004122622 likely benign not specified 2023-10-09 criteria provided, single submitter clinical testing

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