ClinVar Miner

Submissions for variant NM_002294.3(LAMP2):c.205C>T (p.His69Tyr)

gnomAD frequency: 0.00001  dbSNP: rs776875696
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.