ClinVar Miner

Submissions for variant NM_005902.4(SMAD3):c.277C>T (p.Arg93Ter)

gnomAD frequency: 0.00001  dbSNP: rs768713596
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196995 SCV000250776 likely pathogenic not provided 2023-02-22 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); 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
Invitae RCV000473676 SCV000543850 pathogenic Familial thoracic aortic aneurysm and aortic dissection 2023-08-05 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 213781). This variant has not been reported in the literature in individuals affected with SMAD3-related conditions. This variant is present in population databases (rs768713596, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Arg93*) in the SMAD3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMAD3 are known to be pathogenic (PMID: 21778426, 24804794).
Color Diagnostics, LLC DBA Color Health RCV000473676 SCV001352679 pathogenic Familial thoracic aortic aneurysm and aortic dissection 2020-01-08 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 2 of the SMAD3 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/251420 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of SMAD3 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.

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