Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV001542367 | SCV001761059 | uncertain significance | ALG1-congenital disorder of glycosylation | 2020-07-03 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001542367 | SCV003217246 | pathogenic | ALG1-congenital disorder of glycosylation | 2023-04-10 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln436*) in the ALG1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 29 amino acid(s) of the ALG1 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ALG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1184361). This variant disrupts a region of the ALG1 protein in which other variant(s) (p.Arg438Trp) have been determined to be pathogenic (PMID: 20679665, 24157261, 26931382). 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. |