Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000618379 | SCV000735695 | uncertain significance | Cardiovascular phenotype | 2023-02-17 | criteria provided, single submitter | clinical testing | The p.I1791T variant (also known as c.5372T>C), located in coding exon 38 of the LAMA4 gene, results from a T to C substitution at nucleotide position 5372. The isoleucine at codon 1791 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000706232 | SCV000835271 | uncertain significance | Dilated cardiomyopathy 1JJ | 2024-01-20 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1791 of the LAMA4 protein (p.Ile1791Thr). This variant is present in population databases (rs377204776, gnomAD 0.02%). 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: 518608). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Baylor Genetics | RCV000706232 | SCV001528037 | uncertain significance | Dilated cardiomyopathy 1JJ | 2018-12-14 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Mayo Clinic Laboratories, |
RCV002261132 | SCV002542214 | uncertain significance | not provided | 2021-12-02 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000706232 | SCV002797635 | uncertain significance | Dilated cardiomyopathy 1JJ | 2021-08-10 | criteria provided, single submitter | clinical testing | |
| Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000706232 | SCV004176514 | uncertain significance | Dilated cardiomyopathy 1JJ | 2023-02-14 | criteria provided, single submitter | clinical testing | The missense c.5393T>C (p.Ile1798Thr) variant in LAMA4 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ile1798Thr variant is reported with an allele frequency of 0.004% in the gnomAD exomes database and is novel (not in any individuals) in 1000 Genomes database. This variant has been reported to the ClinVar database as Uncertain Significance (multiple submissions). The amino acid change p.Ile1798Thr in LAMA4 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Ile at position 1798 is changed to a Thr changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987623 | SCV004803372 | likely benign | not specified | 2024-01-15 | criteria provided, single submitter | clinical testing |