Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001957662 | SCV002217367 | pathogenic | Multiple gastrointestinal atresias | 2022-02-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TTC7A-related conditions. This variant is present in population databases (rs762466884, gnomAD 0.005%). This sequence change creates a premature translational stop signal (p.Val441Glufs*57) in the TTC7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TTC7A are known to be pathogenic (PMID: 23830146, 24292712). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155441 | SCV003844732 | likely pathogenic | Gastrointestinal defect and immunodeficiency syndrome | 2023-02-02 | criteria provided, single submitter | clinical testing | Variant summary: TTC7A c.1322_1323delTG (p.Val441GlufsX57) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic in ClinVar and are associated with multiple intestinal atresia in HGMD. The variant allele was found at a frequency of 2e-05 in 250454 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1322_1323delTG in individuals affected with Gastrointestinal Defects And Immunodeficiency Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |