ClinVar Miner

Submissions for variant NM_000094.4(COL7A1):c.4012G>A (p.Gly1338Arg)

dbSNP: rs1156352791
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biomedical Innovation Departament, CIEMAT RCV001352811 SCV001547306 pathogenic Epidermolysis bullosa dystrophica 2019-12-15 criteria provided, single submitter research
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV001823199 SCV002072998 likely pathogenic Recessive dystrophic epidermolysis bullosa criteria provided, single submitter clinical testing The missense variant p.G1338R in COL7A1 (NM_000094.3) has been reported before in compound heterozygote form with an invariant spilce mutations in recessive epidermolysis bullosa (Almaani N et al). The variant has been submitted to ClinVar as Pathogenic but no details are provided for an independent assesment. The variant has been previously observed in homozygous state in a patient with epidermolysis bullosa evaluated at our laboratory. The glycine substituion occurs in the triple hellical domain. The p.G1338R variant is observed in 1(0.003%) allele in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.G1338R missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glycine residue at codon 1338 of COL7A1 is conserved in all mammalian species. The nucleotide c.4012 in COL7A1 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002499708 SCV002810893 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 2021-12-17 criteria provided, single submitter clinical testing
Invitae RCV002548488 SCV003525545 pathogenic not provided 2023-09-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the triple helix domain of COL7A1. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236), and variants at these glycine residues in COL7A1 are more frequently observed in individuals with disease than in the general population (PMID: 22058051). However, the clinical significance of this observation remains uncertain since only a limited number of affected individuals have been described to date. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1048010). This missense change has been observed in individual(s) with autosomal recessive dystrophic epidermolysis bullosa (PMID: 19665875, 34435747). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1338 of the COL7A1 protein (p.Gly1338Arg).

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