ClinVar Miner

Submissions for variant NM_000228.3(LAMB3):c.1365_1366del (p.Asn456fs)

gnomAD frequency: 0.00004  dbSNP: rs769967565
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169387 SCV000220778 likely pathogenic Junctional epidermolysis bullosa gravis of Herlitz 2014-10-09 criteria provided, single submitter literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586480 SCV000695998 pathogenic Junctional epidermolysis bullosa, non-Herlitz type 2016-12-30 criteria provided, single submitter clinical testing Variant summary: The LAMB3 c.1365_1366delCA (p.Asn456Argfs) variant results in a premature termination codon, predicted to cause a truncated or absent LAMB3 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was observed in controls with an allele frequency of 2/120648 (1/60324), which does not exceed the estimated maximal expected allele frequency for a pathogenic LAMB3 variant of 1/1517. Multiple publications have reported the variant in affected individuals as compound heterozygotes. In addition, a clinical diagnostic laboratory cites the variant as "likely pathogenic." Therefore, the variant of interest has been classified as "Pathogenic."
Invitae RCV001222091 SCV001394173 pathogenic not provided 2023-11-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn456Argfs*7) 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 (rs769967565, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with autosomal recessive junctional epidermolysis bullosa (PMID: 11023379, 22931927). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 189004). For these reasons, this variant has been classified as Pathogenic.
Centogene AG - the Rare Disease Company RCV000169387 SCV002059583 pathogenic Junctional epidermolysis bullosa gravis of Herlitz 2021-04-28 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001222091 SCV003827047 pathogenic not provided 2021-11-18 criteria provided, single submitter clinical testing

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