Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003556045 | SCV004292699 | pathogenic | not provided | 2024-03-12 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 2798 of the COL7A1 protein (p.Met2798Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive dystrophic epidermolysis bullosa (PMID: 8513326). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17423). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL7A1 protein function. This variant disrupts the p.Met2798 amino acid residue in COL7A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 34435747). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000018969 | SCV005077570 | likely pathogenic | Recessive dystrophic epidermolysis bullosa | 2024-04-03 | criteria provided, single submitter | clinical testing | Variant summary: COL7A1 c.8393T>A (p.Met2798Lys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 230376 control chromosomes. c.8393T>A has been reported in the literature in individuals affected with Dystrophic Epidermolysis Bullosa, Recessive (Christiano_1993). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 8513326). ClinVar contains an entry for this variant (Variation ID: 17423). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV005025071 | SCV005662018 | 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 | 2024-04-05 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000018969 | SCV000039256 | pathogenic | Recessive dystrophic epidermolysis bullosa | 1993-05-01 | no assertion criteria provided | literature only |