Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000410724 | SCV000486869 | likely pathogenic | Junctional epidermolysis bullosa gravis of Herlitz | 2016-08-26 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001383024 | SCV001582032 | pathogenic | not provided | 2023-11-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ile669Lysfs*14) in the LAMC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LAMC2 are known to be pathogenic (PMID: 11907499, 16473856). This variant is present in population databases (rs778012079, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with junctional epidermolysis bullosa (PMID: 16473856). This variant is also known as 2006del7. ClinVar contains an entry for this variant (Variation ID: 371316). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222499 | SCV002500666 | likely pathogenic | Junctional epidermolysis bullosa | 2022-03-27 | criteria provided, single submitter | clinical testing | Variant summary: LAMC2 c.2006_2012delTTTCAGA (p.Ile669LysfsX14) 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 not been observed at our laboratory but have been reported in the HGMD database. The variant allele was found at a frequency of 8e-06 in 251332 control chromosomes. c.2006_2012delTTTCAGA has been reported in the literature in at-least one homozygous individual affected with Herlitz Junctional Epidermolysis Bullosa (example, Varki_2006). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |