ClinVar Miner

Submissions for variant NM_000094.3(COL7A1):c.5532+1G>A (rs767182886)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000579227 SCV000680735 pathogenic not provided 2017-11-29 criteria provided, single submitter clinical testing The c.5532+1 G>A splice site variant has been previously reported as an apparently de novo variant in association with autosomal recessive DEB (Mellerio et al., 1999; Shipman et al., 2014). This variant destroys the canonical splice donor site in intron 64, and is expected to cause abnormal gene splicing. The variant is not observed in large population cohorts (Lek et al., 2016). In summary, we consider this variant to be pathogenic.
Undiagnosed Diseases Network,NIH RCV000626021 SCV000746631 pathogenic Recessive dystrophic epidermolysis bullosa 2018-03-07 criteria provided, single submitter clinical testing
Invitae RCV000579227 SCV001575674 likely pathogenic not provided 2020-08-09 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 64 of the COL7A1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs767182886, ExAC 0.01%). Disruption of this splice site has been observed in individual(s) with clinical features of epidermolysis bullosa dystrophica (PMID: 10383749, 22209565). ClinVar contains an entry for this variant (Variation ID: 488825). 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). 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.
Natera, Inc. RCV001272354 SCV001454266 pathogenic Epidermolysis bullosa dystrophica inversa, autosomal recessive 2020-09-16 no assertion criteria provided clinical testing

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