Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Otolaryngology – Head & Neck Surgery, |
RCV001375406 | SCV001571887 | uncertain significance | Hearing impairment | 2021-04-12 | criteria provided, single submitter | clinical testing | PM2_Moderate, PP3_Supporting |
Invitae | RCV001871974 | SCV002127765 | uncertain significance | not provided | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 28 of the COL9A1 protein (p.Arg28Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs745566207, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with COL9A1-related conditions. 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 COL9A1 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. |