Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001201706 | SCV001372791 | uncertain significance | Bethlem myopathy 1 | 2023-08-14 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs539057609, gnomAD 0.002%). 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) performed at Invitae indicates that this missense variant is not expected to disrupt COL6A3 protein function. ClinVar contains an entry for this variant (Variation ID: 933482). This variant has not been reported in the literature in individuals affected with COL6A3-related conditions. This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 543 of the COL6A3 protein (p.Tyr543His). |