Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002037657 | SCV002233061 | pathogenic | Danon disease | 2021-03-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the c.928G nucleotide in the LAMP2 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 16217705, 15673802, 29753918, 19373884, 29753918). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with clinical features of Danon disease (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with leucine at codon 310 of the LAMP2 protein (p.Val310Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine. This variant also falls at the last nucleotide of exon 7, which is part of the consensus splice site for this exon. |