Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000651443 | SCV000773294 | uncertain significance | Dilated cardiomyopathy 1JJ | 2023-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 507 of the LAMA4 protein (p.Arg507Gln). This variant is present in population databases (rs146358872, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 541226). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
ARUP Laboratories, |
RCV000651443 | SCV001471593 | uncertain significance | Dilated cardiomyopathy 1JJ | 2019-08-01 | criteria provided, single submitter | clinical testing | The LAMA4 c.1520G>A; p.Arg507Gln variant (rs146358872), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 541226). This variant is found in the African population with an overall allele frequency of 0.04% (10/24968 alleles) in the Genome Aggregation Database. The arginine at codon 507 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, due to limited information, the clinical significance of the p.Arg507Gln variant is uncertain at this time. |
Gene |
RCV001756094 | SCV001996730 | uncertain significance | not provided | 2019-11-04 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 541226; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function |
Ambry Genetics | RCV002388138 | SCV002708167 | uncertain significance | Cardiovascular phenotype | 2021-11-24 | criteria provided, single submitter | clinical testing | The p.R507Q variant (also known as c.1520G>A), located in coding exon 11 of the LAMA4 gene, results from a G to A substitution at nucleotide position 1520. The arginine at codon 507 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, glutamine is the reference amino acid in other 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. |
Fulgent Genetics, |
RCV000651443 | SCV002794059 | uncertain significance | Dilated cardiomyopathy 1JJ | 2021-07-13 | criteria provided, single submitter | clinical testing |