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

dbSNP: rs1553612617

Total submissions: 2

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