Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV003468192 | SCV004197310 | likely pathogenic | ALG6-congenital disorder of glycosylation 1C | 2023-05-19 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003468192 | SCV004330176 | pathogenic | ALG6-congenital disorder of glycosylation 1C | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 14 of the ALG6 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALG6-related conditions. 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. This variant disrupts a region of the ALG6 protein in which other variant(s) (p.Gln464*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |