ClinVar Miner

Submissions for variant NM_003239.4(TGFB3):c.488G>A (p.Arg163Gln) (rs920721092)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520464 SCV000618936 uncertain significance not provided 2018-02-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TGFB3 gene. The R163Q variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R163Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution occurs at a position that is conserved across species. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, R163Q lacks sufficient evidence, including observation in a significant number of affected individuals, segregation studies, and functional characterization, that would further clarify its potential pathogenicity.
Invitae RCV000465880 SCV000550894 uncertain significance Loeys-Dietz syndrome 4 2016-09-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 163 of the TGFB3 protein (p.Arg163Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TGFB3-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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