ClinVar Miner

Submissions for variant NM_000094.3(COL7A1):c.5820G>A (p.Pro1940=) (rs200972872)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000763114 SCV000893656 likely pathogenic Recessive dystrophic epidermolysis bullosa; Pretibial epidermolysis bullosa; Dominant dystrophic epidermolysis bullosa with absence of skin; Transient bullous dermolysis of the newborn; Epidermolysis bullosa pruriginosa; Nail disorder, nonsyndromic congenital, 8; Generalized dominant dystrophic epidermolysis bullosa 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000497540 SCV000589317 pathogenic not provided 2018-11-01 criteria provided, single submitter clinical testing The c.5820 G>A variant in the COL7A1 gene has been reported previously with another COL7A1 variant in association with recessive dystrophic epidermolysis bullosa (RDEB) (Teracina et al., 1998, Gardella et al. 2002). This variant reduces the quality of the splice donor site in intron 70, and is expected to cause abnormal gene splicing and exon skipping of exon 70, resulting in an internally deleted protein (Terracina et al. 1998). The c.5820 G>A variant is observed in 23/126,384 (0.018%) alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016). We interpret c.5820 G>A as a pathogenic variant.
Invitae RCV000497540 SCV000934821 pathogenic not provided 2018-12-22 criteria provided, single submitter clinical testing This sequence change affects codon 1940 of the COL7A1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the COL7A1 protein. This variant also falls at the last nucleotide of exon 70 of the COL7A1 coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs200972872, ExAC 0.02%). This variant has been observed to segregate with disease in a family affected with epidermolysis bullosa dystrophica (PMID: 9804332). ClinVar contains an entry for this variant (Variation ID: 431810). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 9804332). For these reasons, this variant has been classified as Pathogenic.

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.