ClinVar Miner

Submissions for variant NM_000494.4(COL17A1):c.332-1G>A

gnomAD frequency: 0.00001  dbSNP: rs754289857
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000432540 SCV000517206 pathogenic not provided 2015-05-28 criteria provided, single submitter clinical testing The c.332-1G>A variant in the COL17A1 gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. This splice site change destroys the canonicalsplice acceptor site in intron 5. It is predicted to cause abnormal gene splicing, either leading to an abnormalmessage that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the messageis used for protein translation. The c.332-1G>A change was not observed in approximately 6500 individuals ofEuropean and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not acommon benign variant in these populations. In summary, we interpret c.332-1G>A as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000432540 SCV004475231 likely pathogenic not provided 2023-01-25 criteria provided, single submitter clinical testing 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. This variant has not been reported in the literature in individuals affected with COL17A1-related conditions. This sequence change affects an acceptor splice site in intron 5 of the COL17A1 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 COL17A1 are known to be pathogenic (PMID: 16473856, 17344927, 20301304, 21357940, 24319098). This variant is present in population databases (rs754289857, gnomAD 0.007%). ClinVar contains an entry for this variant (Variation ID: 379785). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.
GenomeConnect, ClinGen RCV001824762 SCV002074862 not provided Junctional epidermolysis bullosa no assertion provided phenotyping only Variant interpreted as Pathogenic and reported on 06-21-2015 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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