ClinVar Miner

Submissions for variant NM_000228.3(LAMB3):c.978del (p.Phe327fs)

gnomAD frequency: 0.00002  dbSNP: rs763559509
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.