ClinVar Miner

Submissions for variant NM_000094.3(COL7A1):c.682+1G>A (rs775288140)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413063 SCV000490480 pathogenic not provided 2018-10-24 criteria provided, single submitter clinical testing The c.682+1G>A pathogenic variant in the COL7A1 gene has been reported numerous times previously in association with RDEB (Kern et al., 2006, 2009, Gardella et al. 2002, Hovnanian et al. 1997, Abu Sa'd 2006, Drera et al., 2009, Jerabkova et al., 2010). This splice site variant destroys the canonical splice donor site in intron 5. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.682+1G>A variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.682+1G>A as a pathogenic variant.
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000503323 SCV000588375 likely pathogenic Recessive dystrophic epidermolysis bullosa 2017-06-18 criteria provided, single submitter clinical testing
Invitae RCV000413063 SCV000938241 pathogenic not provided 2018-10-16 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 5 of the COL7A1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with epidermolysis bullosa (PMID: 9326325, 19643583, 18951764, 11000732, 22266148). ClinVar contains an entry for this variant (Variation ID: 372329). 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL7A1 are known to be pathogenic (PMID: 16971478). For these reasons, this variant has been classified as Pathogenic.

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