Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000674594 | SCV000799958 | likely pathogenic | Junctional epidermolysis bullosa gravis of Herlitz | 2018-05-15 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226366 | SCV003922574 | likely pathogenic | Junctional epidermolysis bullosa | 2023-03-24 | criteria provided, single submitter | clinical testing | Variant summary: LAMB3 c.1486-1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. On in-silico tool, TraP predicts its possibly damaging. The variant allele was found at a frequency of 4.1e-06 in 245098 control chromosomes. To our knowledge, no occurrence of c.1486-1G>A in individuals affected with Junctional Epidermolysis Bullosa and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV003768011 | SCV004674458 | likely pathogenic | not provided | 2023-06-19 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with LAMB3-related conditions. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 558343). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change affects an acceptor splice site in intron 12 of the LAMB3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LAMB3 are known to be pathogenic (PMID: 11023379, 16473856). |
| Baylor Genetics | RCV000674594 | SCV001162872 | likely pathogenic | Junctional epidermolysis bullosa gravis of Herlitz | no assertion criteria provided | clinical testing |