Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004582240 | SCV005066363 | pathogenic | not provided | 2023-11-10 | criteria provided, single submitter | clinical testing | This variant results in the deletion of exons 43-62 and part of exon 63 (c.4482+35_5462del) of the COL7A1 gene. It is expected to disrupt splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL7A1 are known to be disease-causing for autosomal recessive dystrophic epidermolysis bullosa (PMID: 16971478). However, certain variants affecting donor or acceptor splice sites in the triple helical domain of COL7A1 are expected to result in in-frame exon skipping and have been reported to cause autosomal dominant dystrophic epidermolysis bullosa (PMID: 31670143). This variant has not been observed in the literature in individuals with autosomal recessive COL7A1-related conditions. This variant has been reported in individual(s) with clinical features of autosomal dominant epidermolysis bullosa (Invitae); however, the role of the variant in this condition is currently unclear. This variant disrupts a region of the COL7A1 protein in which other variant(s) (p.Gly1661Arg) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |