Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000219177 | SCV000270330 | likely benign | not specified | 2015-07-16 | criteria provided, single submitter | clinical testing | p.Asp115Asn in exon 4 of LAMA4: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, 3 mammals (star-nosed mole, cape elephent shrew, aardvark) have an asparagi ne (Asn) at this position despite high nearby amino acid conservation. In additi on, computational prediction tools do not suggest a high likelihood of impact to the protein. This variant has been identified in 1/66678 European chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). |
Invitae | RCV000555552 | SCV000654012 | uncertain significance | Dilated cardiomyopathy 1JJ | 2023-11-04 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 115 of the LAMA4 protein (p.Asp115Asn). This variant is present in population databases (rs781919095, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 227477). 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. 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. |
Ambry Genetics | RCV002453760 | SCV002615201 | uncertain significance | Cardiovascular phenotype | 2019-11-01 | criteria provided, single submitter | clinical testing | The p.D115N variant (also known as c.343G>A), located in coding exon 3 of the LAMA4 gene, results from a G to A substitution at nucleotide position 343. The aspartic acid at codon 115 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well conserved in available 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. |