Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003064512 | SCV003443786 | likely pathogenic | Amyloidosis, hereditary systemic 1 | 2022-03-08 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 126 of the TTR protein (p.Thr126Asn). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) (PMID: 17503405). This variant is also known as Thr106Asn. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TTR protein function. 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. |