ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.465_471dup (p.Ser158fs)

dbSNP: rs958818801
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000473672 SCV000543787 uncertain significance Aortic valve disease 2 2023-12-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser158Argfs*147) in the SMAD6 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SMAD6 cause disease. This variant is present in population databases (no rsID available, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with SMAD6-related conditions (PMID: 31138930, 32499606, 34953066). This variant is also known as c.454_455insCGGCGGG:p.P152fs. ClinVar contains an entry for this variant (Variation ID: 405520). 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.
GeneDx RCV002464200 SCV002758955 uncertain significance not provided 2022-11-30 criteria provided, single submitter clinical testing Identified in an individual with nonsyndromic radioulnar synostosis (Yang et al., 2019); Frameshift variant predicted to result in protein truncation, as the last 339 amino acids are replaced with 146 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; This variant is associated with the following publications: (PMID: 34953066, 31138930, 32499606)
The Laboratory of Genetics and Metabolism, Hunan Children’s Hospital RCV000851342 SCV000993646 likely pathogenic Radioulnar synostosis 2019-05-14 no assertion criteria provided case-control PVS1, PM2, PP4

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.