Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003064554 | SCV003443171 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2022-04-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 631 of the TMEM67 protein (p.Gln631His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TMEM67-related conditions. 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV004963364 | SCV005524974 | uncertain significance | Inborn genetic diseases | 2024-06-26 | criteria provided, single submitter | clinical testing | The c.1893G>C (p.Q631H) alteration is located in exon 19 (coding exon 19) of the TMEM67 gene. This alteration results from a G to C substitution at nucleotide position 1893, causing the glutamine (Q) at amino acid position 631 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV005050707 | SCV005682356 | uncertain significance | COACH syndrome 1; Joubert syndrome 6; Meckel syndrome, type 3; RHYNS syndrome; Bardet-Biedl syndrome 14; Nephronophthisis 11 | 2024-05-14 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004733563 | SCV005364894 | uncertain significance | TMEM67-related disorder | 2024-08-21 | no assertion criteria provided | clinical testing | The TMEM67 c.1893G>C variant is predicted to result in the amino acid substitution p.Gln631His. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |