Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002240222 | SCV001216369 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2019-11-26 | 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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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 been observed in individual(s) with clinical features of Ehlers-Danlos syndrome (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with cysteine at codon 478 of the COL5A1 protein (p.Gly478Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. |
| Mendelics | RCV002240222 | SCV002516279 | likely pathogenic | Ehlers-Danlos syndrome, classic type, 1 | 2022-05-04 | criteria provided, single submitter | clinical testing |