Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000485788 | SCV000567298 | pathogenic | not provided | 2015-08-07 | criteria provided, single submitter | clinical testing | The R81X variant in the LAMB3 gene has been reported previously in association with junctionalepidermolysis bullosa in the homozygous state and in an individual who was also heterozygous for theE210K variant (Castori et al., 2008; Mellerio et al., 1998). This variant is predicted to cause loss ofnormal protein function either through protein truncation or nonsense-mediated mRNA decay. The R81Xvariant was not observed in approximately 6,500 individuals of European and African American ancestryin the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.We interpret R81X as a pathogenic variant. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001269275 | SCV001448611 | pathogenic | Junctional epidermolysis bullosa | 2020-11-13 | criteria provided, single submitter | clinical testing | Variant summary: LAMB3 c.241C>T (p.Arg81X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251454 control chromosomes (gnomAD). c.241C>T has been reported in the literature in individuals affected with Junctional Epidermolysis Bullosa (Mellerio_1998, Castori_2008, Hammersen_2016). 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. One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Biomedical Innovation Departament, |
RCV001269275 | SCV001547453 | pathogenic | Junctional epidermolysis bullosa | 2011-06-21 | criteria provided, single submitter | research | |
| Labcorp Genetics |
RCV000485788 | SCV002226523 | pathogenic | not provided | 2024-10-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg81*) in the LAMB3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LAMB3 are known to be pathogenic (PMID: 11023379, 16473856). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with junctional epidermolysis bullosa (PMID: 9767254). ClinVar contains an entry for this variant (Variation ID: 419475). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV005018797 | SCV005645139 | pathogenic | Amelogenesis imperfecta type 1A; Junctional epidermolysis bullosa gravis of Herlitz; Junctional epidermolysis bullosa, non-Herlitz type | 2024-03-30 | criteria provided, single submitter | clinical testing |