Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002231334 | SCV000631603 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2017-07-01 | 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. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with COL5A2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 1293 of the COL5A2 protein (p.Ala1293Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. |
| Prevention |
RCV003409780 | SCV004112411 | uncertain significance | COL5A2-related condition | 2023-01-26 | criteria provided, single submitter | clinical testing | The COL5A2 c.3878C>T variant is predicted to result in the amino acid substitution p.Ala1293Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-189904045-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |