Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000556725 | SCV000639589 | uncertain significance | ALG2-congenital disorder of glycosylation; Congenital myasthenic syndrome 14 | 2023-12-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser352Leufs*3) in the ALG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 65 amino acid(s) of the ALG2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALG2-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001844193 | SCV002104030 | uncertain significance | not specified | 2022-02-07 | criteria provided, single submitter | clinical testing | Variant summary: ALG2 c.1055_1056delinsTGA (p.Ser352LeufsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein in the Glycosyl transferase, family 1 domain (IPR001296). Although this truncation is not predicted to cause absense of the protein through nonsense mediated decay, and truncations downstream of this position have been classified as uncertain significance in ClinVar (1053713), the variant may potentially alter protein function by altering the last 65 amino acids in the protein sequence. The variant was absent in 281616 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1055_1056delinsTGA in individuals affected with Congenital Disorder Of Glycosylation, Type 1i and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as of uncertain significance. Based on the evidence outlined above, the variant was classified as VUS. |
| Ambry Genetics | RCV002526120 | SCV003558696 | uncertain significance | Inborn genetic diseases | 2021-03-16 | criteria provided, single submitter | clinical testing | Not expected to trigger nonsense-mediated mRNA decay Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |