ClinVar Miner

Submissions for variant NM_000371.3(TTR):c.160A>G (p.Arg54Gly)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000817566 SCV000958133 likely pathogenic Amyloidogenic transthyretin amyloidosis 2018-08-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 54 of the TTR protein (p.Arg54Gly). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with vitreous amyloidosis in a family (PMID: 22187309) and has been observed in an individual affected with familial amyloid polyneuropathy (PMID: 22973891) and in a family with amyloidosis (Invitae). This variant is also known as Arg34Gly in the literature. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). Variants that disrupt the p.Arg54 amino acid residue in TTR have been observed in affected individuals (PMID: 22745357, 21692911, 9605286). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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