ClinVar Miner

Submissions for variant NM_000228.3(LAMB3):c.430C>T (p.Arg144Ter)

gnomAD frequency: 0.00001  dbSNP: rs759518184
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000578521 SCV000680541 pathogenic not provided 2021-05-12 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; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 8624605, 27375110, 25525159, 8824879, 29946029, 11023379, 31589614)
Invitae RCV000578521 SCV001398595 pathogenic not provided 2023-12-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg144*) 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 (rs759518184, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with junctional epidermolysis bullosa (PMID: 8824879, 11023379, 27375110). ClinVar contains an entry for this variant (Variation ID: 488703). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Biomedical Innovation Departament, CIEMAT RCV001352730 SCV001547455 pathogenic Junctional epidermolysis bullosa 2016-12-01 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001352730 SCV002555664 pathogenic Junctional epidermolysis bullosa 2022-06-06 criteria provided, single submitter clinical testing Variant summary: LAMB3 c.430C>T (p.Arg144X) 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 250998 control chromosomes. c.430C>T has been reported in the literature in individuals affected with Junctional Epidermolysis Bullosa. These data indicate that the variant may be associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Counsyl RCV000984193 SCV001132243 pathogenic Junctional epidermolysis bullosa gravis of Herlitz 2014-01-02 no assertion criteria provided clinical testing

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