Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000483352 | SCV000574090 | uncertain significance | not provided | 2017-03-14 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the LAMA4 gene. The R214C variant has not been published as pathogenic or been reported as benign to our knowledge. The R214C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, this substitution occurs at a position that is not conserved across species. Additionally, this variant is observed in 3/16470 (0.02%) alleles from individuals of South Asian ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). |
Invitae | RCV002525966 | SCV003496947 | uncertain significance | Dilated cardiomyopathy 1JJ | 2023-05-16 | 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 424296). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. This variant is present in population databases (rs148801194, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 214 of the LAMA4 protein (p.Arg214Cys). |