Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000579120 | SCV000680543 | pathogenic | not provided | 2022-08-12 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 16473856, 12813757, 8824879, 21801158, 9160387) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169424 | SCV000917571 | pathogenic | Junctional epidermolysis bullosa gravis of Herlitz | 2018-12-10 | criteria provided, single submitter | clinical testing | Variant summary: LAMB3 c.1978C>T (p.Arg660X) 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. The variant allele was found at a frequency of 2.2e-05 in 275670 control chromosomes (gnomAD). c.1978C>T has been reported in the literature in multiple individuals affected with Junctional Epidermolysis Bullosa (Christiano_1997, Yuen_2011, Varki_2006). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV000579120 | SCV000933452 | pathogenic | not provided | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg660*) 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 present in population databases (rs146794392, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with autosomal recessive junctional epidermolysis bullosa (PMID: 9160387, 21801158). ClinVar contains an entry for this variant (Variation ID: 189034). For these reasons, this variant has been classified as Pathogenic. |
Counsyl | RCV000169424 | SCV000220833 | pathogenic | Junctional epidermolysis bullosa gravis of Herlitz | 2016-06-30 | no assertion criteria provided | clinical testing |