Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586284 | SCV000696001 | uncertain significance | not provided | 2017-07-18 | criteria provided, single submitter | clinical testing | Variant summary: The c.947G>A (p.Cys316Tyr) in LAMB3 gene is a missense variant involves a highly conserved nucleotide and 4/4 in silico tools predict deleterious outcome, however no functional studies supporting these predictions were published at the time of evaluation. The variant is located within Laminin-type epidermal growth factor-like domain and alters the first Cys, therefore disrupting one out of four disulfide bonds, required for the proper folding. The c.947G>A is absent from the control population datasets of ExAC and gnomAD (120836 and 246036 chrs tested, respectively). To our knowledge, the variant has not been reported in affected individuals via published reports or cited by reputable databases/clinical laboratories. Taken together, the variant was classified as VUS, until new information becomes available. |
| Neuberg Centre For Genomic Medicine, |
RCV003148801 | SCV004048314 | uncertain significance | Junctional epidermolysis bullosa, non-Herlitz type | criteria provided, single submitter | clinical testing | The missense c.947G>A(p.Cys316Tyr) variant in LAMB3 gene has been submitted to ClinVar as a Variant of Uncertain Significance, but no details are available for independent assessment. It has not been reported in affected individuals. The p.Cys316Tyr variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Cys at position 316 is changed to a Tyr changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Cys316Tyr in LAMB3 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. | |
| Institute of Human Genetics, |
RCV003148801 | SCV003834790 | likely pathogenic | Junctional epidermolysis bullosa, non-Herlitz type | 2022-06-14 | no assertion criteria provided | research |