Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000498204 | SCV000589630 | pathogenic | not provided | 2016-02-08 | criteria provided, single submitter | clinical testing | The c.5701-1 G>T pathogenic variant in the COL7A1 gene has been reported previously in association with RDEB(Chen et al., 2015). This splice site variant destroys the canonical splice acceptor site in intron 67. It is predicted tocause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNAdecay, or to an abnormal protein product if the message is used for protein translation. The c.5701-1 G>T variant wasnot observed in approximately 6500 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. We interpret c.5701-1 G>T asa pathogenic variant. |
Labcorp Genetics |
RCV000498204 | SCV004292730 | pathogenic | not provided | 2023-03-29 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 67 of the COL7A1 gene. It is expected to disrupt RNA 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 pathogenic (PMID: 16971478). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with autosomal dominant epidermolysis bullosa and/or autosomal recessive epidermolysis bullosa dystrophica (PMID: 25566895, 27899325). This variant is also known as IVS67-1G>T. ClinVar contains an entry for this variant (Variation ID: 431992). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |