Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000522246 | SCV000619418 | uncertain significance | not provided | 2019-01-17 | criteria provided, single submitter | clinical testing | The R723C variant in the LAMA4 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R723C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R723C 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. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R723C as a variant of uncertain significance |
Invitae | RCV000794780 | SCV000934210 | uncertain significance | Dilated cardiomyopathy 1JJ | 2022-08-09 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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: 450799). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. This variant is present in population databases (rs782482395, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 723 of the LAMA4 protein (p.Arg723Cys). |