Submissions for variant NM_000094.4(COL7A1):c.7875+1G>C

dbSNP: rs2107637140

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001529592	SCV004292704	likely pathogenic	not provided	2023-12-26	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 105 of the COL7A1 gene. It is expected to disrupt 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 COL7A1 are known to be disease-causing for autosomal recessive dystrophic epidermolysis bullosa (PMID: 16971478). However, certain variants affecting donor or acceptor splice sites in the triple helical domain of COL7A1 are expected to result in in-frame exon skipping and have been reported to cause autosomal dominant dystrophic epidermolysis bullosa (PMID: 31670143). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL7A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1175000). 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529592	SCV001743285	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001529592	SCV001958158	pathogenic	not provided		no assertion criteria provided	clinical testing