Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003578221 | SCV004330308 | uncertain significance | not provided | 2023-03-31 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2394 of the COL7A1 protein (p.Pro2394Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autosomal dominant dystrophic epidermolysis bullosa (PMID: 32396230). It has also been observed to segregate with disease in related individuals. 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) performed at Invitae indicates that this missense variant is not expected to disrupt COL7A1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004801373 | SCV005422984 | uncertain significance | not specified | 2024-10-29 | criteria provided, single submitter | clinical testing | Variant summary: COL7A1 c.7181C>G (p.Pro2394Arg) 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 frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.7181C>G has been reported in the literature in heterozygous individuals affected with Dystrophic epidermolysis bullosa with nails only phenotype (e.g. Yang_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 32396230). ClinVar contains an entry for this variant (Variation ID: 2765184). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |