Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000399329 | SCV000353647 | uncertain significance | Junctional epidermolysis bullosa | 2017-04-28 | criteria provided, single submitter | clinical testing | The LAMB3 c.978delC (p.Phe327LeufsTer69) variant results in a frameshift and is predicted to result in a premature termination of the protein. The p.Phe327LeufsTer69 variant has been reported in one study in which it is found in a compound heterozygous state with a second null variant in one individual with the severe Herlitz form of junctional epidermolysis bullosa (Nakano et al. 2000). Control data are unavailable for this variant which is reported at a frequency of 0.000309 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the potential impact of frameshift variants and the supporting evidence, the p.Phe327LeufsTer69 variant is classified as a variant of unknown significance but suspicious for pathogenicity for junctional epidermolysis bullosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Counsyl | RCV000409820 | SCV000486951 | likely pathogenic | Junctional epidermolysis bullosa gravis of Herlitz | 2016-09-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001850522 | SCV002109327 | pathogenic | not provided | 2023-09-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Phe327Leufs*69) 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 (rs763559509, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with clinical features of autosomal recessive junctional epidermolysis bullosa (PMID: 11023379). ClinVar contains an entry for this variant (Variation ID: 295120). For these reasons, this variant has been classified as Pathogenic. |