Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Nx |
RCV001374699 | SCV001571624 | likely pathogenic | Junctional epidermolysis bullosa gravis of Herlitz | 2019-12-18 | criteria provided, single submitter | clinical testing | This nonsense variant (c.1756C>T) is in a region where loss-of-function is a known mechanism of disease (PVS1). GnomAD databases show this variant to have very low allele frequency (PM2) and in silico models produced pathogenic predictions (PP3). This variant was first reported by Nakano et al. PMID: 11810295 in a female infant heterozygous for c.167insT/c.1756C>T . We interpret c.1756C>T to be likely pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271647 | SCV002555659 | likely pathogenic | Junctional epidermolysis bullosa | 2022-06-01 | criteria provided, single submitter | clinical testing | Variant summary: LAMB3 c.1756C>T (p.Gln586X) 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 allele was found at a frequency of 1.2e-05 in 250296 control chromosomes. c.1756C>T has been reported in the literature in at least one compound heterozygous individual affected with Herlitz Junctional Epidermolysis Bullosa, indicating the variant is likely associated with disease (example Nakano_2002, Varki_2006). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |