Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000393971 | SCV000333778 | uncertain significance | not provided | 2015-09-14 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002514270 | SCV003027817 | pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 786 of the TMEM67 protein (p.Gly786Glu). This variant is present in population databases (rs386834193, gnomAD 0.007%). This missense change has been observed in individual(s) with Meckel syndrome (PMID: 20232449). 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: 56774). 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 TMEM67 protein function with a positive predictive value of 95%. This variant disrupts the p.Gly786 amino acid residue in TMEM67. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31411728). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000050187 | SCV000082597 | probable-pathogenic | Meckel syndrome, type 3 | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |