Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000633666 | SCV000754927 | pathogenic | Multiple gastrointestinal atresias | 2021-03-12 | criteria provided, single submitter | clinical testing | A missense variant downstream of this codon (p.Ala832Thr) has been reported as homozygous in two siblings affected with severe apoptotic enterocolitis and determined to be likely pathogenic (PMID: 24417819). This suggests that disruption of amino acid sequence downstream of codon 824 is likely pathogenic. For these reasons, this variant has been classified as Pathogenic. This variant has been observed in an individual with clinical features of gastrointestinal defects and immunodeficiency syndrome (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs768053395, ExAC 0.002%). This sequence change results in a premature translational stop signal in the TTC7A gene (p.Gln824Profs*11). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 35 amino acids of the TTC7A protein. |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV002291284 | SCV002583828 | uncertain significance | not provided | 2022-08-12 | criteria provided, single submitter | clinical testing | PM2 |