ClinVar Miner

Submissions for variant NM_153704.6(TMEM67):c.2374A>G (p.Arg792Gly)

dbSNP: rs1815059174
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001785366 SCV002026382 uncertain significance Joubert syndrome 6 2021-11-10 criteria provided, single submitter clinical testing _x000D_ Criteria applied: PM3, PM2_SUP, PP3
University of Iowa Renal Genetics Clinic, University of Iowa RCV002478012 SCV002605550 likely pathogenic COACH syndrome 1 2022-04-12 criteria provided, single submitter clinical testing This variant is predicted to result in a single amino acid substitution of Arg to Gly at codon 792 in exon 23 of the TMEM67 gene. It was found in trans with a second TMEM67 variant in a patient with features of COACH syndrome. This variant meets the following ACMG criteria: PM2, PM3, PP2, PP3.
Fulgent Genetics, Fulgent Genetics RCV002478013 SCV002783286 uncertain significance COACH syndrome 1; Joubert syndrome 6; Meckel syndrome, type 3; RHYNS syndrome; Bardet-Biedl syndrome 14; Nephronophthisis 11 2021-09-22 criteria provided, single submitter clinical testing
Invitae RCV003772169 SCV004582054 likely pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome 2023-12-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 792 of the TMEM67 protein (p.Arg792Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Joubert syndrome and related disorders and/or nephronophthisis (PMID: 21068128, 36617405). ClinVar contains an entry for this variant (Variation ID: 1325829). 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%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.