Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000171968 | SCV000050954 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Gene |
RCV000200378 | SCV000250544 | uncertain significance | not specified | 2015-03-03 | criteria provided, single submitter | clinical testing | p.Asp1563Tyr (GAT>TAT): c.4687 G>T in exon 34 of the LAMA4 gene (NM_002290.3). A variant of unknown significance has been identified in the LAMA4 gene. The D1563Y variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The D1563Y variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D1563Y 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 and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in CARDIOMYOPATHY |
Invitae | RCV001205884 | SCV001377164 | uncertain significance | Dilated cardiomyopathy 1JJ | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with tyrosine at codon 1563 of the LAMA4 protein (p.Asp1563Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is not present in population databases (ExAC no frequency). 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: 191680). 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 C15"). 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 | RCV002326944 | SCV002634501 | uncertain significance | Cardiovascular phenotype | 2022-10-05 | criteria provided, single submitter | clinical testing | The p.D1563Y variant (also known as c.4687G>T), located in coding exon 33 of the LAMA4 gene, results from a G to T substitution at nucleotide position 4687. The aspartic acid at codon 1563 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly 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. |