Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001871950 | SCV002255564 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2025-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 11 of the TMEM67 protein (p.Met11Val). This variant is present in population databases (rs758761945, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TMEM67-related conditions. ClinVar contains an entry for this variant (Variation ID: 1050591). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
| Gene |
RCV001358212 | SCV002571390 | uncertain significance | not provided | 2022-03-08 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Fulgent Genetics, |
RCV002486490 | SCV002785565 | uncertain significance | COACH syndrome 1; Joubert syndrome 6; Meckel syndrome, type 3; RHYNS syndrome; Bardet-Biedl syndrome 14; Nephronophthisis 11 | 2022-04-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004968115 | SCV005524968 | uncertain significance | Inborn genetic diseases | 2024-12-04 | criteria provided, single submitter | clinical testing | The c.31A>G (p.M11V) alteration is located in exon 1 (coding exon 1) of the TMEM67 gene. This alteration results from a A to G substitution at nucleotide position 31, causing the methionine (M) at amino acid position 11 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Department of Pathology and Laboratory Medicine, |
RCV001358212 | SCV001553885 | uncertain significance | not provided | no assertion criteria provided | clinical testing |