ClinVar Miner

Submissions for variant NM_000228.3(LAMB3):c.2632C>T (p.Arg878Cys)

gnomAD frequency: 0.00004  dbSNP: rs199946321
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics, Fulgent Genetics RCV002476635 SCV002794300 uncertain significance Amelogenesis imperfecta type 1A; Junctional epidermolysis bullosa gravis of Herlitz; Junctional epidermolysis bullosa, non-Herlitz type 2021-07-30 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001356996 SCV001552313 uncertain significance not provided no assertion criteria provided clinical testing The LAMB3 p.R878C variant was reported in one individual with progressive multifocal leukoencephalopathy (van der Kolk_2016_PMID: 27042682). The variant was not reported in ClinVar, but it was identified in dbSNP (ID: rs199946321). The variant was identified in control databases in 11 of 251482 chromosomes at a frequency of 0.00004374 (Genome Aggregation Database March 6, 2019, v2.1.1). The p.R878 residue is conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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.