ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.465_471del (p.Gly156fs) (rs958818801)

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Total submissions: 3
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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 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. 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 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 current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SMAD6 cause disease. 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 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 RCV000851354 SCV001430997 risk factor Radioulnar synostosis 2020-08-28 no assertion criteria provided literature only

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