Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000493382 | SCV000583346 | uncertain significance | not provided | 2018-10-30 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the TTR gene. The L102F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The L102F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. However, the L102F variant is not observed in large population cohorts (Lek et al., 2016). Additionally, missense variants in nearby residues have been reported in the Human Gene Mutation Database in individuals with TTR-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV001856983 | SCV002151515 | uncertain significance | Amyloidosis, hereditary systemic 1 | 2023-02-18 | criteria provided, single submitter | clinical testing | 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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 430522). 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 leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 102 of the TTR protein (p.Leu102Phe). |