Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519929 | SCV000621383 | uncertain significance | not provided | 2017-10-03 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the LAMA4 gene. The L314P variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016). The L314P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, no missense variants in nearby residues have been reported in the Human Gene Mutation Database (Stenson et al., 2014). |
Invitae | RCV000691209 | SCV000818957 | uncertain significance | Dilated cardiomyopathy 1JJ | 2018-06-22 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with proline at codon 314 of the LAMA4 protein (p.Leu314Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LAMA4-related disease. ClinVar contains an entry for this variant (Variation ID: 452566). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |