Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000494202 | SCV000581972 | uncertain significance | not provided | 2017-05-02 | criteria provided, single submitter | clinical testing | The N257D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N257D variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved, and missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with LAMP2-related disorders (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
| Labcorp Genetics |
RCV001370893 | SCV001567437 | uncertain significance | Danon disease | 2023-07-19 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 257 of the LAMP2 protein (p.Asn257Asp). ClinVar contains an entry for this variant (Variation ID: 429409). 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on LAMP2 protein function. |
| Ambry Genetics | RCV002404289 | SCV002668784 | likely benign | Cardiovascular phenotype | 2024-03-21 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Fulgent Genetics, |
RCV001370893 | SCV002790128 | uncertain significance | Danon disease | 2021-11-18 | criteria provided, single submitter | clinical testing |