Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001244925 | SCV001418181 | uncertain significance | Bethlem myopathy 1 | 2019-10-17 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with serine at codon 429 of the COL6A3 protein (p.Leu429Ser). The leucine residue is moderately conserved and there is a large physicochemical difference between leucine and serine. This variant has not been reported in the literature in individuals with COL6A3-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. |