Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001048654 | SCV001212668 | uncertain significance | Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 | 2023-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 1519 of the COL12A1 protein (p.Lys1519Ile). This variant is present in population databases (rs767232468, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with COL12A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 845564). 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. 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. |