ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.42G>A (p.Trp14Ter) (rs1246889300)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538622 SCV000650591 uncertain significance Loeys-Dietz syndrome 3 2017-05-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 14 (p.Trp14*) of the SMAD6 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SMAD6-related disease. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SMAD6 cause disease. Therefore, this variant has been classified as a Variant of Uncertain Significance.
GeneDx RCV000760748 SCV000890642 likely pathogenic not provided 2018-09-25 criteria provided, single submitter clinical testing The W14X variant in the SMAD6 gene has been reported previously in one individual with severe intellectual disability who also harbored variants in two other genes, one of which was felt to be a possible cause of the phenotype (Gilissen et al., 2014). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The W14X variant is not observed in large population cohorts (Lek et al., 2016). We interpret W14X as a likely pathogenic variant.
Centre of Medical Genetics, University of Antwerp RCV000770952 SCV000854414 pathogenic Aortic valve disorder 2018-11-14 no assertion criteria provided research
OMIM RCV000787045 SCV000925961 pathogenic Aortic valve disease 2 2019-07-08 no assertion criteria provided literature only

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