Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000791469 | SCV000930720 | uncertain significance | Aortic valve disease 2 | 2019-07-15 | criteria provided, single submitter | clinical testing | 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. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SMAD6 cause disease. This variant has been observed in an individual affected with sagittal craniosynostosis as well as his unaffected parent. In addition, the affected individual had a de novo variant in another gene related to craniosynostosis, indicating that the SMAD6 variant was not the primary cause of disease (PMID: 28808027). This variant has also been observed in an individual with bicuspid aortic valve associated thoracic aortic aneurysm (PMID: 28659821). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. 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. |
| Gene |
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) |
| The Laboratory of Genetics and Metabolism, |
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, |
RCV001849446 | SCV002106419 | pathogenic | Craniosynostosis syndrome | 2018-01-01 | no assertion criteria provided | literature only |