Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001569082 | SCV001793071 | pathogenic | not provided | 2021-02-17 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in GeneDX; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27666369) |
Revvity Omics, |
RCV001569082 | SCV002016851 | likely pathogenic | not provided | 2021-05-12 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001569082 | SCV004292995 | pathogenic | not provided | 2024-02-24 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 155 of the TBCE protein (p.Ile155Asn). This variant is present in population databases (rs780472451, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of progressive encephalopathy with amyotrophy and optic atrophy (PMID: 27666369). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 372201). 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 TBCE protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000412509 | SCV000490274 | pathogenic | Encephalopathy, progressive, with amyotrophy and optic atrophy | 2016-11-29 | no assertion criteria provided | literature only |