Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000190573 | SCV000245592 | likely pathogenic | Junctional epidermolysis bullosa, non-Herlitz type | 2014-12-18 | criteria provided, single submitter | clinical testing | The c.2435-6_2440del variant in COL17A1 has not been previously reported in individuals/any other families with disease. Data from large population studies is insufficient to assess the frequency of this variant. This variant deletes the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Homozygous or compound heterozygous loss of function variants in COL17A1 have been shown to cause junctional epidermolysis bullosa. In summary, although additional studies are required to fully establish its clinical significance, the c.2435-6_2440del variant is likely pathogenic. |
Invitae | RCV003765208 | SCV004694177 | likely pathogenic | not provided | 2023-10-04 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 35 (c.2435-6_2440del) of the COL17A1 gene. It is expected to disrupt RNA 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 COL17A1 are known to be pathogenic (PMID: 16473856, 17344927, 20301304, 21357940, 24319098). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL17A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 208569). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |