Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000170533 | SCV000807224 | uncertain significance | Multiple gastrointestinal atresias | 2017-09-01 | criteria provided, single submitter | clinical testing | This variant was found once in our laboratory in trans with a pathogenic variant (c.1001+3_1001+6delAAGT) in a 12-year-old female with intestinal disease with epithelial dysplasia, chronic diarrhea with malabsorption, hypogammaglobulinemia, lymphopenia. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226234 | SCV003923149 | pathogenic | Gastrointestinal defect and immunodeficiency syndrome | 2023-03-05 | criteria provided, single submitter | clinical testing | Variant summary: TTC7A c.211G>A (p.Glu71Lys) results in a conservative amino acid change located in the Tetratricopeptide repeat protein 7, N-terminal domain (IPR045819) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251454 control chromosomes. c.211G>A has been reported in the literature in multiple individuals affected with features of Primary Immunodeficiency Diseases (PIDs) such as Gastrointestinal Defects And Immunodeficiency Syndrome (example, PMID: 32084423, 32888943, 27577878, 24417819, 28936210). These data indicate that the variant is very likely to be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV000170533 | SCV004263970 | pathogenic | Multiple gastrointestinal atresias | 2023-09-01 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects TTC7A function (PMID: 24417819). For these reasons, this variant has been classified as 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 TTC7A protein function. ClinVar contains an entry for this variant (Variation ID: 190395). This missense change has been observed in individual(s) with TTC7A-related conditions (PMID: 24417819, 25174867, 27418642). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs147914967, gnomAD 0.004%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 71 of the TTC7A protein (p.Glu71Lys). |
| Gene |
RCV004589829 | SCV005079686 | pathogenic | not provided | 2024-02-14 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate this variant has a deleterious effect on protein function including impaired adhesion to collagen and fibronectin and increased apoptosis (PMID: 24417819); This variant is associated with the following publications: (PMID: 31787977, 24417819, 27577878, 25174867, 30455981, 33122718, 34985046, 29879038, 33457482, 27418642, 34975848, 35627206, 31743734, 32084423, 30553809, 32888943, 28936210, 25534311, Ngan2014[paper], Culbreath2022[paper]) |
| OMIM | RCV004562394 | SCV000223098 | pathogenic | Gastrointestinal defects and immunodeficiency syndrome 1 | 2014-12-01 | no assertion criteria provided | literature only |