Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002049135 | SCV002309222 | likely pathogenic | Amyloidosis, hereditary systemic 1 | 2023-03-23 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1524375). 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. 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. This variant is also known as p.His90Asp. This missense change has been observed in individual(s) with clinical features of hereditary transthyretin-mediated amyloidosis (PMID: 17554795, 25430583; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 110 of the TTR protein (p.His110Asp). |
| Ambry Genetics | RCV002324505 | SCV002606029 | uncertain significance | Cardiovascular phenotype | 2020-12-29 | criteria provided, single submitter | clinical testing | The p.H110D variant (also known as c.328C>G), located in coding exon 3 of the TTR gene, results from a C to G substitution at nucleotide position 328. The histidine at codon 110 is replaced by aspartic acid, an amino acid with similar properties. This variant has been detected in multiple amyloidosis cohorts, including two affected individuals from the same family (Benson MD et al. Muscle Nerve, 2007 Oct;36:411-23; Jimenez-Zepeda VH et al. Amyloid, 2015 Mar;22:26-30; Carr AS et al. J Neurol Neurosurg Psychiatry, 2016 Jun;87:620-7; Rowczenio D et al. Hum Mutat, 2019 01;40:90-96). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |