Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000198503 | SCV000250560 | uncertain significance | not provided | 2022-12-21 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function |
Ambry Genetics | RCV000621022 | SCV000737148 | uncertain significance | Cardiovascular phenotype | 2022-07-15 | criteria provided, single submitter | clinical testing | The p.R1521H variant (also known as c.4562G>A), located in coding exon 32 of the LAMA4 gene, results from a G to A substitution at nucleotide position 4562. The arginine at codon 1521 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
Invitae | RCV000651437 | SCV000773288 | uncertain significance | Dilated cardiomyopathy 1JJ | 2021-11-09 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 213607). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1521 of the LAMA4 protein (p.Arg1521His). This variant is present in population databases (rs782805733, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. 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. |