ClinVar Miner

Submissions for variant NM_005902.4(SMAD3):c.802C>T (p.Arg268Cys) (rs794727798)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000179456 SCV000231708 pathogenic not provided 2015-10-27 criteria provided, single submitter clinical testing
GeneDx RCV000235212 SCV000250758 uncertain significance not specified 2017-02-28 criteria provided, single submitter clinical testing R268C was reported as a variant of uncertain significance in at least one individual tested for TAAD-related disorders in an external database (Landrum et al., 2014). The R268C variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R268C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, missense variants in nearby residues (F248L, T261I, P263L) have been reported in HGMD in association with TAAD-related disorders (Stenson et al., 2014). Lastly, functional studies conducted by Stroschein et al. (1999), showed that R268C decreased the binding activity and the ability of R268C to mediate transcription activation of the TGFß-signaling pathway.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000179456 SCV001808492 likely pathogenic not provided no assertion criteria provided clinical testing

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