Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV001195330 | SCV001365676 | likely benign | not specified | 2019-09-27 | criteria provided, single submitter | clinical testing | The p.Asp475Asn variant in LAMA4 is classified as likely benign due to a lack of conservation across species. Greater than 5 mammals carry an aspartic acid (Asn) at this position despite high nearby amino acid conservation. ACMG/AMP Criteria applied: BP4_Strong. |
Gene |
RCV001553113 | SCV001773923 | uncertain significance | not provided | 2019-03-22 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function |
Invitae | RCV001876265 | SCV002247684 | uncertain significance | Dilated cardiomyopathy 1JJ | 2022-06-27 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. ClinVar contains an entry for this variant (Variation ID: 929968). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. This variant is present in population databases (rs782319667, gnomAD 0.002%). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 475 of the LAMA4 protein (p.Asn475Asp). |
Ambry Genetics | RCV002393449 | SCV002702694 | uncertain significance | Cardiovascular phenotype | 2022-10-21 | criteria provided, single submitter | clinical testing | The p.N475D variant (also known as c.1423A>G), located in coding exon 11 of the LAMA4 gene, results from an A to G substitution at nucleotide position 1423. The asparagine at codon 475 is replaced by aspartic acid, an amino acid with highly similar properties. 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. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |