ClinVar Miner

Submissions for variant NM_000094.4(COL7A1):c.7474C>T (p.Arg2492Ter)

dbSNP: rs765529435
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biomedical Innovation Departament, CIEMAT RCV001352863 SCV001547377 pathogenic Epidermolysis bullosa dystrophica 2018-05-03 criteria provided, single submitter research
Center for Research in Genodermatoses and Epidermolysis Bullosa, University of Buenos Aires RCV002276706 SCV002499360 pathogenic Recessive dystrophic epidermolysis bullosa 2022-03-14 criteria provided, single submitter clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute 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, LabCorp 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).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.