Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biomedical Innovation Departament, |
RCV001352863 | SCV001547377 | pathogenic | Epidermolysis bullosa dystrophica | 2018-05-03 | criteria provided, single submitter | research | |
Center for Research in Genodermatoses and Epidermolysis Bullosa, |
RCV002276706 | SCV002499360 | pathogenic | Recessive dystrophic epidermolysis bullosa | 2022-03-14 | criteria provided, single submitter | clinical testing | |
Victorian Clinical Genetics Services, |
RCV002276706 | SCV003921906 | pathogenic | Recessive dystrophic epidermolysis bullosa | 2022-04-01 | criteria provided, single submitter | clinical testing | 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with dystrophic epidermolysis bullosa (OMIM, PMID: 31670143). (I) 0108 - This gene is associated with both recessive and dominant disease. The spectrum of dystrophic epidermolysis bullosa associated with this gene can be either autosomal dominant or recessive inheritance. Autosomal dominant epidermolysis bullosa dystrophica (MIM#131750) is typically associated with milder phenotypes, whereas autosomal recessive epidermolysis bullosa dystrophica (MIM#226600) is usually observed in more severe cases (OMIM). Premature termination variants resulting in complete absence of protein are usually associated with the most severe recessive dystrophic epidermolysis bullosa (PMID: 32506467). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 (2 heterozygotes, 0 homozygotes). (SP) 0701 - Other premature termination variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Many NMD-predicted variants in this gene have been reported as likely pathogenic/pathogenic (ClinVar). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported in many individuals with autosomal recessive dystrophic epidermolysis bullosa (PMIDs: 12485454, 16965329, 24252097, 31786163, 32484238). (SP) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003331128 | SCV004039237 | pathogenic | COL7A1-related disorders | 2023-08-24 | criteria provided, single submitter | clinical testing | Variant summary: COL7A1 c.7474C>T (p.Arg2492X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8e-06 in 251366 control chromosomes (i.e., 2 heterozygotes; gnomAD v2.1 Exomes dataset). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.7474C>T has been reported in the literature in individuals affected with Dystrophic Epidermolysis Bullosa, Recessive (e.g., Gardella_2002, Robertson_2021). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 12485454, 34230977). Three submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV003558822 | SCV004292707 | pathogenic | not provided | 2023-06-23 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1048050). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with autosomal recessive dystrophic epidermolysis bullosa (PMID: 12485454, 32484238, 33274474). This variant is present in population databases (rs765529435, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg2492*) in the COL7A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL7A1 are known to be pathogenic (PMID: 16971478). |