Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001857350 | SCV002243839 | pathogenic | Amyloidosis, hereditary systemic 1 | 2021-09-21 | criteria provided, single submitter | clinical testing | This variant is also known as Val30Gly. ClinVar contains an entry for this variant (Variation ID: 13465). 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. Experimental studies have shown that this missense change affects TTR function (PMID: 15820680). This variant disrupts the p.Val50 amino acid residue in TTR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22620962, 22745357, 23833285, 24455802, 24555660, 26115788). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. This missense change has been observed in individual(s) with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) (PMID: 9066351, 24613567). It has also been observed to segregate with disease in related individuals. This sequence change replaces valine with glycine at codon 50 of the TTR protein (p.Val50Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is not present in population databases (ExAC no frequency). |
| OMIM | RCV001857350 | SCV000034656 | pathogenic | Amyloidosis, hereditary systemic 1 | 1997-03-01 | no assertion criteria provided | literature only |