Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001850576 | SCV002254783 | likely pathogenic | not provided | 2024-03-21 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 7 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 present in population databases (rs147734242, gnomAD 0.4%). 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: 298750). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Fulgent Genetics, |
RCV005025448 | SCV005662696 | likely pathogenic | Epithelial recurrent erosion dystrophy; Epidermolysis bullosa, junctional 4, intermediate | 2024-06-17 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV005025448 | SCV006055262 | likely pathogenic | Epithelial recurrent erosion dystrophy; Epidermolysis bullosa, junctional 4, intermediate | 2023-05-09 | criteria provided, single submitter | research | |
| Prevention |
RCV004742374 | SCV005354177 | uncertain significance | COL17A1-related disorder | 2024-09-28 | no assertion criteria provided | clinical testing | The COL17A1 c.415+2T>G variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.41% of alleles in individuals of Ashkenazi Jewish descent in gnomAD, which is relatively common for an undocumented cause of disease. Loss-of-function variants, including canonical splice variants, are typically associated with autosomal recessive disease. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |