ClinVar

Description

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. This variant disrupts the p.Val52 amino acid residue in TTR. Other variant(s) that disrupt this residue have been observed in individuals with TTR-related conditions (PMID: 14627687), which suggests that this may be a clinically significant amino acid residue. 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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). This variant has been observed in individual(s) with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) (PMID: 15793844, 17484624, 30685801, 29524093, 24101130). This variant is also known as p.Val32Ala. ClinVar contains an entry for this variant (Variation ID: 944589). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 52 of the TTR protein (p.Val52Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine.