Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001755338 | SCV002005480 | uncertain significance | not provided | 2020-09-25 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not observed at a significant frequency in large population cohorts (Lek et al., 2016) |
| Labcorp Genetics |
RCV002544160 | SCV003502625 | uncertain significance | Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 | 2022-10-08 | criteria provided, single submitter | clinical testing | 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. 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) has been performed at Invitae 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 COL12A1 protein function. ClinVar contains an entry for this variant (Variation ID: 1315676). This variant has not been reported in the literature in individuals affected with COL12A1-related conditions. This variant is present in population databases (rs780638272, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 2022 of the COL12A1 protein (p.Thr2022Ser). |