Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000250661 | SCV000319002 | uncertain significance | Cardiovascular phenotype | 2021-01-07 | criteria provided, single submitter | clinical testing | The p.V357M variant (also known as c.1069G>A), located in coding exon 8 of the LAMP2 gene, results from a G to A substitution at nucleotide position 1069. The valine at codon 357 is replaced by methionine, an amino acid with highly similar properties. Based on data from gnomAD, the A allele has an overall frequency of 0.005% (1/ 21992) total alleles studied, with 0 hemizygotes observed. The highest observed frequency was 0.009% (1/10842) of non-Finnish European alleles This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV001037366 | SCV001200776 | uncertain significance | Danon disease | 2022-09-13 | 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 expected to disrupt LAMP2 protein function. ClinVar contains an entry for this variant (Variation ID: 263725). This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.009%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 357 of the LAMP2 protein (p.Val357Met). |