ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.2T>C (p.Met1Thr)

dbSNP: rs1409145798
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001751787 SCV002005049 likely pathogenic not provided 2024-09-11 criteria provided, single submitter clinical testing Identified in a proband and father with bilateral radioulnar synostosis; this variant was also identified in the reportedly unaffected paternal grandmother (PMID: 34953066); Initiation codon variant 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: 34953066)
CeGaT Center for Human Genetics Tuebingen RCV001751787 SCV004132723 uncertain significance not provided 2023-06-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003533007 SCV004280624 uncertain significance Aortic valve disease 2 2024-01-17 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the SMAD6 mRNA. The next in-frame methionine is located at codon 93. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with SMAD6-related conditions (PMID: 34953066). ClinVar contains an entry for this variant (Variation ID: 1174559). 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 RCV001799781 SCV001739403 pathogenic Polydactyly; Radioulnar synostosis 2020-06-20 no assertion criteria provided research

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