Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002006071 | SCV002268907 | uncertain significance | Congenital myasthenic syndrome 15 | 2021-08-25 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 2 of the ALG14 gene. It does not directly change the encoded amino acid sequence of the ALG14 protein. It affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ALG14-related conditions. Nucleotide substitutions within 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, but this prediction has not been confirmed by published transcriptional studies. 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 | RCV002592558 | SCV003628647 | uncertain significance | Inborn genetic diseases | 2022-08-08 | criteria provided, single submitter | clinical testing | The c.288+4A>G intronic alteration results from an A to G substitution 4 nucleotides after coding exon 2 in the ALG14 gene. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Genome- |
RCV002006071 | SCV004049485 | uncertain significance | Congenital myasthenic syndrome 15 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003348719 | SCV004049486 | uncertain significance | Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003348720 | SCV004049487 | uncertain significance | Myopathy, epilepsy, and progressive cerebral atrophy | 2023-04-11 | criteria provided, single submitter | clinical testing |