Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001293567 | SCV001482172 | pathogenic | Sialidosis | 2021-02-11 | criteria provided, single submitter | clinical testing | Variant summary: NEU1 c.1021C>T (p.Arg341X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic in other databases. The variant allele was found at a frequency of 8.1e-06 in 246350 control chromosomes. c.1021C>T has been reported in the literature in individuals affected with Sialidosis (e.g. Coutinho_2012, Han_2020). These data indicate that the variant is associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Fulgent Genetics, |
RCV002499537 | SCV002813965 | likely pathogenic | Sialidosis type 2 | 2022-04-21 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003574876 | SCV004344301 | pathogenic | not provided | 2023-10-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg341*) in the NEU1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 75 amino acid(s) of the NEU1 protein. This variant is present in population databases (rs751458617, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with sialidosis (PMID: 21214877, 32453490). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 997915). This variant disrupts a region of the NEU1 protein in which other variant(s) (p.Arg347Gln) have been determined to be pathogenic (PMID: 25600812; 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. |