Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001049648 | SCV001213713 | likely pathogenic | Familial amyloid neuropathy | 2022-11-29 | criteria provided, single submitter | clinical testing | 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.Glu109 amino acid residue in TTR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1301926, 10842705, 20209591, 25644864, 28635949, 28911993). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 846359). This variant has not been reported in the literature in individuals affected with TTR-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 109 of the TTR protein (p.Glu109Val). |
| Athena Diagnostics | RCV001288935 | SCV001476393 | uncertain significance | not provided | 2020-03-19 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002445262 | SCV002611908 | likely pathogenic | Cardiovascular phenotype | 2020-06-12 | criteria provided, single submitter | clinical testing | The p.E109V variant (also known as c.326A>T and E89V), located in coding exon 3 of the TTR gene, results from an A to T substitution at nucleotide position 326. The glutamic acid at codon 109 is replaced by valine, an amino acid with dissimilar properties. This variant was not reported in the gnomAD database, with coverage at this position. In addition, this alteration is predicted to be deleterious by in silico analysis. Two disease-causing mutations, p.E109Q and p.E109K, have been described in the same codon in individuals with TTR amyloidosis (Barreiros AP et al. Liver Transpl., 2010 Mar;16:314-23; Coelho T et al. Curr Med Res Opin. 2013;29(1):63-76; Rapezzi C. et al. Eur Heart J. 2013;34(7):520-8, Castaño A, et al. Heart Fail Rev 2015 Mar; 20(2):163-78). Based on the majority of available evidence to date, the p.E109V variant is likely to be pathogenic. |