Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001915435 | SCV002177408 | uncertain significance | Danon disease | 2022-10-18 | criteria provided, single submitter | clinical testing | 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) performed at Invitae indicates that this missense variant is not expected to disrupt LAMP2 protein function. ClinVar contains an entry for this variant (Variation ID: 1399201). This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. This variant is present in population databases (rs775416221, gnomAD 0.004%), including at least one homozygous and/or hemizygous individual. This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 356 of the LAMP2 protein (p.Asn356Ser). |
Ambry Genetics | RCV003303335 | SCV004001846 | uncertain significance | Cardiovascular phenotype | 2023-05-22 | criteria provided, single submitter | clinical testing | The p.N356S variant (also known as c.1067A>G), located in coding exon 8 of the LAMP2 gene, results from an A to G substitution at nucleotide position 1067. The asparagine at codon 356 is replaced by serine, an amino acid with highly similar properties. Based on data from gnomAD, the G allele has an overall frequency of 0.0016% (3/183378) total alleles studied, with 1 hemizygote observed. The highest observed frequency was 0.0036% (1/27398) of Latino/Admixed American alleles. This amino acid position is not well 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. |