ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.465_471del (p.Gly156fs)

dbSNP: rs958818801
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000791469 SCV000930720 uncertain significance Aortic valve disease 2 2024-03-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly156Valfs*23) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with sagittal craniosynostosis, bicuspid aortic valve-associated thoracic aortic aneurysm and/or radioulnar synostosis (PMID: 28659821, 28808027, 31138930). ClinVar contains an entry for this variant (Variation ID: 638816). 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 RCV002255165 SCV002526501 uncertain significance not provided 2022-06-15 criteria provided, single submitter clinical testing Reported in a patient with craniosynostosis who also harbored an additional potentially disease-causing variant in the TCF12 gene (Timberlake et al., 2017); Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene or region of a gene for which loss of function is not a well-established mechanism of disease.; This variant is associated with the following publications: (PMID: 28659821, 30038786, 31138930, 28808027)
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues RCV005256466 SCV005909252 likely pathogenic Craniosynostosis 7 2025-03-27 criteria provided, single submitter clinical testing
The Laboratory of Genetics and Metabolism, Hunan Children’s Hospital RCV000851354 SCV000993658 uncertain significance Radioulnar synostosis 2019-05-14 no assertion criteria provided case-control PVS1, PM2, PP4, BS4
OMIM RCV002508149 SCV001430997 risk factor Radioulnar synostosis, nonsyndromic, susceptibility to 2020-08-28 no assertion criteria provided literature only
Yale Center for Mendelian Genomics, Yale University RCV001849446 SCV002106419 pathogenic Craniosynostosis syndrome 2018-01-01 no assertion criteria provided literature only

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.