Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002381247 | SCV002671616 | likely pathogenic | Cardiovascular phenotype | 2022-10-04 | criteria provided, single submitter | clinical testing | The c.741+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 5 of the LAMP2 gene. This alteration has been reported in three individuals with Danon disease (Nishino I et al. Nature, 2000 Aug;406:906-10). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. In addition, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV000010658 | SCV003445769 | pathogenic | Danon disease | 2022-03-22 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 5 of the LAMP2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 10972294). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 9977). Disruption of this splice site has been observed in individuals with Danon disease (PMID: 10972294). |
| OMIM | RCV000010658 | SCV000030884 | pathogenic | Danon disease | 2000-08-24 | no assertion criteria provided | literature only |