Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000689835 | SCV000817504 | uncertain significance | Dilated cardiomyopathy 1JJ | 2023-07-25 | criteria provided, single submitter | clinical testing | Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. ClinVar contains an entry for this variant (Variation ID: 569252). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. This variant is present in population databases (rs782528136, gnomAD 0.008%). This sequence change falls in intron 31 of the LAMA4 gene. It does not directly change the encoded amino acid sequence of the LAMA4 protein. It affects a nucleotide within the consensus splice site. |
| Ambry Genetics | RCV003303123 | SCV003988571 | uncertain significance | Cardiovascular phenotype | 2023-05-31 | criteria provided, single submitter | clinical testing | The c.4266+4A>G intronic variant results from an A to G substitution 4 nucleotides after coding exon 30 in the LAMA4 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |