ClinVar Miner

Submissions for variant NM_000094.4(COL7A1):c.4767del (p.Asp1590fs)

dbSNP: rs1057517721
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414689 SCV000490488 pathogenic not provided 2022-05-24 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10504458, 19814614, 19665875)
Labcorp Genetics (formerly Invitae), Labcorp RCV000414689 SCV003525228 pathogenic not provided 2022-04-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 372335). This premature translational stop signal has been observed in individual(s) with Hallopeau-Siemens recessive dystrophic epidermolysis bullosa (PMID: 10504458). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp1590Thrfs*120) in the COL7A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL7A1 are known to be pathogenic (PMID: 16971478).
Breakthrough Genomics, Breakthrough Genomics RCV004596175 SCV005088894 pathogenic Epidermolysis bullosa 2021-03-30 criteria provided, single submitter clinical testing This variant is predicted to cause a frameshift and consequent premature termination of the protein and the resultant protein will likely to lack BPTI/Kunitz inhibitor domain, nonhelical region and cell attachment motif of the protein[Uniprot]; this will likely result in loss-of-function. Due to the introduction of a premature stop codon, this aberrant transcript will likely be targeted by the nonsense-mediated mRNA decay (NMD) mechanism [PMID: 15040442]. The identified variant was previously (represented as 4767delA) reported in recessive dystrophic epidermolysis bullosa (RDEB) patients and was classified as pathogenic [PMID: 10504458,18558993].

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.