ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.223C>T (p.Arg75Ter)

dbSNP: rs1595756640
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001766764 SCV002008726 pathogenic not provided 2024-05-08 criteria provided, single submitter clinical testing De novo variant with confirmed parentage in a patient referred for genetic testing at GeneDx; however, the reported clinical features are only partially consistent with the features typically observed in individuals with pathogenic variants in this gene; Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31138930, 34328347)
Labcorp Genetics (formerly Invitae), Labcorp RCV002536179 SCV002953765 uncertain significance Aortic valve disease 2 2022-05-30 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. ClinVar contains an entry for this variant (Variation ID: 690410). This premature translational stop signal has been observed in individual(s) with SMAD6-related conditions (PMID: 31138930). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg75*) 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, Hunan Children’s Hospital RCV000851345 SCV000993649 pathogenic Radioulnar synostosis 2019-05-14 no assertion criteria provided case-control PVS1, PM2, PP3, PP4

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