Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001236613 | SCV001409345 | uncertain significance | Danon disease | 2019-08-27 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with LAMP2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in the last intron (intron 8) of the LAMP2 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. |
| Ambry Genetics | RCV003380919 | SCV004097152 | uncertain significance | Cardiovascular phenotype | 2023-06-22 | criteria provided, single submitter | clinical testing | The c.1094-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 9 of the LAMP2 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on data from gnomAD, the C allele has an overall frequency of <0.01% (1/22016) total alleles studied, with 1 hemizygote(s) observed. The highest observed frequency was 0.02% (1/5913) of African alleles. This alteration occurs at the 3' terminus of theLAMP2 gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts <0.01% of the protein. The exact functional effect of this alteration is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |