Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001218537 | SCV001390423 | uncertain significance | Danon disease | 2023-12-16 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 69 of the LAMP2 protein (p.His69Tyr). This variant is present in population databases (rs776875696, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 947454). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LAMP2 protein function with a negative predictive value of 80%. 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. |
Ambry Genetics | RCV002418750 | SCV002724758 | uncertain significance | Cardiovascular phenotype | 2020-09-29 | criteria provided, single submitter | clinical testing | The p.H69Y variant (also known as c.205C>T), located in coding exon 3 of the LAMP2 gene, results from a C to T substitution at nucleotide position 205. The histidine at codon 69 is replaced by tyrosine, an amino acid with similar properties. Based on data from gnomAD, the T allele has an overall frequency of 0.001% (2/183342) total alleles studied, with 0 hemizygote(s) observed. The highest observed frequency was 0.007% (2/27395) of Latino alleles. 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. |