ClinVar Miner

Submissions for variant NM_005902.4(SMAD3):c.871G>A (p.Gly291Arg)

dbSNP: rs730880215
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001359513 SCV001555387 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-05-17 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 291 of the SMAD3 protein (p.Gly291Arg). This variant also falls at the last nucleotide of exon 6, which is part of the consensus splice site for this exon. This variant is present in population databases (rs730880215, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of SMAD3-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 180525). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Blueprint Genetics RCV000157502 SCV000207247 likely pathogenic Loeys-Dietz syndrome 2014-07-18 no assertion criteria provided clinical testing

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