ClinVar Miner

Submissions for variant NM_000094.4(COL7A1):c.3265C>T (p.Gln1089Ter)

dbSNP: rs1553612617
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000578178 SCV000680021 likely pathogenic Recessive dystrophic epidermolysis bullosa 2017-08-30 criteria provided, single submitter clinical testing The NM_000094.3(COL7A1):c.3265C>T heterozygous nonsense variant was identified in exon 24 of COL7A1. This nonsense variant introduces a stop codon at amino acid position 1089, NP_000085.1(COL7A1):p.(Gln1089*). This variant is predicted to result in loss of protein function either through truncation (>50% of the protein, including multiple triple helix repeats) or nonsense-mediated decay. This variant is not present in the gnomAD population database and has not been previously observed in other clinical cases. However, other truncating variants downstream of c.3265C>T in COL7A1 have been reported as pathogenic in individuals with dystrophic epidermolysis bullosa (ClinVar). Based on current information and in association with the NM_000094.3(COL7A1):c.1732C>T nonsense variant, this variant has been classified as LIKELY PATHOGENIC. The presence of these two nonsense variants suggests a possible compound heterozygous mode of inheritance which is consistent with dystrophic epidermolysis bullosa.
Division of Human Genetics, National Health Laboratory Service/University of the Witwatersrand RCV003403367 SCV004123065 pathogenic Epidermolysis bullosa 2023-07-01 criteria provided, single submitter research
Neuberg Centre For Genomic Medicine, NCGM RCV000578178 SCV005400718 likely pathogenic Recessive dystrophic epidermolysis bullosa 2023-06-22 criteria provided, single submitter clinical testing The observed stop gain c.3265C>T(p.Gln1089Ter) variant in COL7A1 gene variant has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.3265C>T variant is absent in gnomAD Exomes database. This variant has been reported to the ClinVar database as Likely pathogenic. Computational evidence (MutationTaster - Disease causing) predict damaging effect on protein structure and function for this variant. The nucleotide change c.3265C>T in COL7A1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005034148 SCV005664236 likely pathogenic Recessive dystrophic epidermolysis bullosa; Pretibial dystrophic epidermolysis bullosa; Dominant dystrophic epidermolysis bullosa with absence of skin; Transient bullous dermolysis of the newborn; Epidermolysis bullosa pruriginosa; Nonsyndromic congenital nail disorder 8; Generalized dominant dystrophic epidermolysis bullosa 2024-03-13 criteria provided, single submitter clinical testing

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