ClinVar Miner

Submissions for variant NM_005902.4(SMAD3):c.278G>A (p.Arg93Gln)

dbSNP: rs863223765
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001705120 SCV000250795 uncertain significance not provided 2021-03-11 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 213800; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 23139211, 29543232)
Invitae RCV000234145 SCV000289108 pathogenic Familial thoracic aortic aneurysm and aortic dissection 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 93 of the SMAD3 protein (p.Arg93Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with SMAD3-related disease (PMID: 29543232; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 213800). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is expected to disrupt SMAD3 function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000234145 SCV000902145 likely pathogenic Familial thoracic aortic aneurysm and aortic dissection 2022-02-25 criteria provided, single submitter clinical testing
Institute of Human Genetics, Cologne University RCV003445690 SCV004174149 likely pathogenic Aneurysm-osteoarthritis syndrome 2023-11-03 criteria provided, single submitter clinical testing

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