Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000037412 | SCV000061069 | pathogenic | Danon disease | 2015-03-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000157963 | SCV000207898 | pathogenic | not provided | 2017-04-06 | criteria provided, single submitter | clinical testing | p.Trp98Ter (TGG>TAG): c.293 G>A in exon 3 of the LAMP2 gene (NM_002294.2). The Trp98Ter mutation in the LAMP2 gene has been reported previously in association with Danon disease (Fanin M et al., 2006; Boucek D et al., 2011; Miani D et al., 2012). Fanin et al. (2006) reported the Trp98Stop mutation in a male patient presenting with jaundice at age 12 who developed muscle weakness, Wolff-Parkinson-White (WPW) syndrome and hypertrophic cardiomyopathy by his 20s. His mother, who was heterozygous for Trp98Stop, had a history of WPW, mild muscle weakness and hypertrophic cardiomyopathy progressing to heart failure with subsequent heart transplant by age 52. Additionally, skeletal muscle from this male patient demonstrated near absence of LAMP2 protein, while his mother's LAMP2 protein levels were not significantly different from controls, highlighting the variability between males who harbor hemizygous mutations and female heterozygous carriers (Fanin M et al., 2006). Moreover, the Trp98Stop mutation is predicted to cause loss of normal protein function either through premature protein truncation or nonsense-mediated mRNA decay. Therefore, Trp98Stop in the LAMP2 gene is interpreted to be a disease-causing mutation. The variant is found in HCM panel(s). |
| Labcorp Genetics |
RCV000037412 | SCV002140654 | pathogenic | Danon disease | 2021-01-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This nonsense change has been observed in individual(s) with clinical features of Danon disease (PMID: 16565504). ClinVar contains an entry for this variant (Variation ID: 44423). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp98*) in the LAMP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LAMP2 are known to be pathogenic (PMID: 21415759). |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000157963 | SCV000925118 | pathogenic | not provided | 2013-01-31 | no assertion criteria provided | provider interpretation |