Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001850191 | SCV002228828 | pathogenic | not provided | 2021-06-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Disruption of this splice site ‚Äãhas been observed in individual(s) with autosomal recessive dystrophic epidermolysis bullosa (PMID: 10504458, 28830826). ClinVar contains an entry for this variant (Variation ID: 180695) This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 53 of the COL7A1 gene. 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). |
Strand Center for Genomics and Personalized Medicine, |
RCV000157650 | SCV000195855 | likely pathogenic | Recessive dystrophic epidermolysis bullosa | 2014-06-05 | no assertion criteria provided | clinical testing | This COL7A1 splice site variant c.4980+1G>C was found heterozygously in a 5 year male suffering from epidermolysis bullosa. This change results in the substitution and consecutive loss of an essential splice donor site and complete loss of the NC-2 domain. The variant overlaps with a known splice site variant c.4980+1G>T that was found to the associated with dystrophic epidermolysis bullosa and seen in compound heterozygosity in a patient with Hallopeau-Siemens recesive dystrophic epidermolysis bullosa (PMID:10504458). |