ClinVar Miner

Submissions for variant NM_003239.4(TGFB3):c.859C>T (p.Arg287Trp) (rs757774610)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756774 SCV000884684 uncertain significance not provided 2018-03-21 criteria provided, single submitter clinical testing The TGFB3: p.Arg287Trp variant (rs757774610) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.02 percent in the Latino population (identified on 8 out of 34,418 chromosomes). The arginine at position 287 is highly conserved up to zebrafish considering 12 species (Alamut v2.10) and computational analyses of the p.Arg287Trp variant on protein structure and function indicate a deleterious effect (SIFT: damaging, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Arg287Trp variant with certainty.
Invitae RCV000824473 SCV000965372 uncertain significance Loeys-Dietz syndrome 4 2018-10-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 287 of the TGFB3 protein (p.Arg287Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs757774610, ExAC 0.009%). This variant has not been reported in the literature in individuals with TGFB3-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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