Submissions for variant NM_000094.4(COL7A1):c.6994C>T (p.Arg2332Ter)

gnomAD frequency: 0.00001  dbSNP: rs765027608

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001218750	SCV001390648	pathogenic	not provided	2024-03-01	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg2332*) 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). This variant is present in population databases (rs765027608, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with autosomal recessive dystrophic epidermolysis bullosa (PMID: 28830826, 33274474). This variant has been reported in individual(s) with autosomal dominant dystrophic epidermolysis bullosa (PMID: 34046686); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 947637). For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM	RCV004789480	SCV005400958	pathogenic	Epidermolysis bullosa pruriginosa	2023-06-22	criteria provided, single submitter	clinical testing	The observed stop gained variant c.6994C>T(p.Arg2332Ter) in the COL7A1 gene has been reported previously in individuals affected with autosomal recessive and autosomal dominant dystrophic epidermolysis bullosa (Vahidnezhad H, et al., 2017; Yu Y, et al., 2021). This variant is absent in the gnomAD Exomes. It is submitted to ClinVar as Pathogenic. Computational evidence (MutationTaster - Disease causing) predicts damaging effect on protein structure and function for this variant. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV005036479	SCV005664150	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	2024-03-20	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001218750	SCV001740912	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001218750	SCV001960087	pathogenic	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001828739	SCV002079208	pathogenic	Epidermolysis bullosa dystrophica	2020-11-10	no assertion criteria provided	clinical testing