Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV001810067 | SCV002058907 | pathogenic | Craniosynostosis 7 | 2022-01-03 | criteria provided, single submitter | clinical testing | Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). The variant has been reported to be associated with SMAD6 related disorder (PMID:28808027). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Labcorp Genetics |
RCV001882574 | SCV002314133 | uncertain significance | Aortic valve disease 2 | 2021-10-28 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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. This variant is also known as c.264dupC (p.G88fs*33). This premature translational stop signal has been observed in individual(s) with craniosynostosis (PMID: 28808027). This sequence change creates a premature translational stop signal (p.Arg91Glufs*30) 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. |
| The Laboratory of Genetics and Metabolism, |
RCV001799789 | SCV001739412 | pathogenic | Radioulnar synostosis | 2020-06-20 | no assertion criteria provided | research |