Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000778785 | SCV000915156 | uncertain significance | Sialidosis type 2 | 2017-09-15 | criteria provided, single submitter | clinical testing | The NEU1 c.45G>A (p.Trp15Ter) stop-gained variant has been reported in a compound heterozygous state with a splice site variant in one individual with mucolipidosis type 1 presenting as severe nonimmune fetal hydrops (Loren et al. 2005). The patient's parents were each heterozgyous for one of the identified variants. Biochemical analyses revealed significant elevation of sialic acid in the patient's lymphocytes and skin fibroblasts as well as massive excretion of sialic acid in urine. α-neuraminidase activity in fibroblasts from the patient was also less than one percent of the control value. Control data are unavailable for the p.Trp15Ter variant, which is reported at a frequency of 0.000016 in the European (non-Finnish) population of the Exome Aggregation Consortium. However, this frequency is based on one allele in a region of good sequence coverage. Therefore, the variant is presumed to be rare. Based on the available evidence and the potential impact of stop-gained variants, the p.Trp15Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for mucolipidosis type 1. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Labcorp Genetics |
RCV001204075 | SCV001375264 | pathogenic | not provided | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp15*) in the NEU1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NEU1 are known to be pathogenic (PMID: 11063730, 14517945). This variant is present in population databases (rs768711214, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with sialidosis (PMID: 15908988). ClinVar contains an entry for this variant (Variation ID: 631977). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002234170 | SCV002511502 | pathogenic | Sialidosis | 2022-04-18 | criteria provided, single submitter | clinical testing | Variant summary: NEU1 c.45G>A (p.Trp15X) 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 by our laboratory. The variant allele was found at a frequency of 4.1e-06 in 245416 control chromosomes. c.45G>A has been reported in the literature in at-least one individual affected with Sialidosis (example, Loren_2005). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and one laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |