Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000154739 | SCV000204419 | uncertain significance | not specified | 2013-04-03 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Asn735Ser varia nt in LAMA4 has not been reported in the literature nor previously identified by our laboratory. This variant has been identified in 1/8600 European American ch romosomes and 1/4406 African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). Asparagine ( Asn) at position 735 is not conserved in mammals or evolutionarily distant speci es and 1 mammal (dog) carries a serine (Ser; this variant), raising the possibil ity that this change may be tolerated. In addition, other computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) also sugges t that this variant may not impact the protein, though this information is not p redictive enough to rule out pathogenicity. Although this data supports that the Asn735Ser variant may be benign, additional studies are needed to fully assess its clinical significance. |
Invitae | RCV000807747 | SCV000947817 | uncertain significance | Dilated cardiomyopathy 1JJ | 2022-04-02 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. This variant is present in population databases (rs374279330, gnomAD 0.01%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 735 of the LAMA4 protein (p.Asn735Ser). ClinVar contains an entry for this variant (Variation ID: 178054). 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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. |
Ambry Genetics | RCV002426745 | SCV002728205 | uncertain significance | Cardiovascular phenotype | 2021-07-22 | criteria provided, single submitter | clinical testing | The p.N735S variant (also known as c.2204A>G), located in coding exon 17 of the LAMA4 gene, results from an A to G substitution at nucleotide position 2204. The asparagine at codon 735 is replaced by serine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
Fulgent Genetics, |
RCV000807747 | SCV002784120 | uncertain significance | Dilated cardiomyopathy 1JJ | 2021-08-23 | criteria provided, single submitter | clinical testing |