Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000651441 | SCV000773292 | uncertain significance | Dilated cardiomyopathy 1JJ | 2023-03-19 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 541224). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. This variant is present in population databases (rs782618132, gnomAD 0.009%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 418 of the LAMA4 protein (p.Lys418Asn). |
Gene |
RCV001731844 | SCV001981908 | uncertain significance | not provided | 2023-06-12 | 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 | RCV002422406 | SCV002678094 | uncertain significance | Cardiovascular phenotype | 2023-01-22 | criteria provided, single submitter | clinical testing | The p.K418N variant (also known as c.1254G>T), located in coding exon 10 of the LAMA4 gene, results from a G to T substitution at nucleotide position 1254. The lysine at codon 418 is replaced by asparagine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and asparagine 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. |