Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000462750 | SCV000549127 | likely benign | Danon disease | 2023-11-07 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002411475 | SCV002673273 | uncertain significance | Cardiovascular phenotype | 2020-03-12 | criteria provided, single submitter | clinical testing | The p.H260Y variant (also known as c.778C>T), located in coding exon 6 of the LAMP2 gene, results from a C to T substitution at nucleotide position 778. The histidine at codon 260 is replaced by tyrosine, an amino acid with similar properties. This alterations has been reported in sudden cardiac death and Danon disease cohorts (Campuzano O et al. Sports Med, 2017 Oct;47:2101-2115; López-Sainz Á et al. Rev Esp Cardiol (Engl Ed), 2018 Aug). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Victorian Clinical Genetics Services, |
RCV000462750 | SCV002769047 | uncertain significance | Danon disease | 2020-06-11 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3C-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0110 - This gene is known to be associated with X-linked dominant disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from a histidine to a tyrosine (exon 6). (N) 0253 - Variant is hemizygous. (N) 0302 - Variant is present in gnomAD <0.001 for a dominant condition (3 heterozygotes, 2 hemizygotes, 0 homozygotes). (P) 0503 - Missense variant consistently predicted to be tolerated or not conserved in mammals with a minor amino acid change. (B) 0600 - Variant is located in an annotated domain or motif (Lysosome-associated membrane glycoprotein; PDB, NCBI). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0808 - Previous reports of pathogenicity are conflicting. The variant has been previously reported as pathogenic in patients with HCM (PMID: 30108015), and also reported as a VUS in patients with HCM and arrhythmia (ClinVar, PMID: 28771489, 30847666). (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |