Submissions for variant NM_000094.4(COL7A1):c.2308_2314+1del

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004766890	SCV005381018	likely pathogenic	Recessive dystrophic epidermolysis bullosa	2024-08-15	criteria provided, single submitter	clinical testing	Variant summary: COL7A1 c.2308_2314+1delAGGACTGG disrupts a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing and loss of COL7A1 function. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. Two predict the variant creates a 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 249348 control chromosomes. To our knowledge, no occurrence of c.2308_2314+1delAGGACTGG in individuals affected with Dystrophic Epidermolysis Bullosa, Recessive and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.