Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001806089 | SCV002050780 | pathogenic | Fucosidosis | 2021-12-06 | criteria provided, single submitter | clinical testing | Variant summary: FUCA1 c.1216G>T (p.Gly406X) 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. One truncation (p.Gln427X) downstream of this position has been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251452 control chromosomes (genomAD). c.1216G>T has been reported in one literature in two homozygous individuals affected with Fucosidosis in two unrelated families (Seo_1995). Both exhibited slowly progressive neurological deterioration by the age of 3 years and Alpha-L-fucosidase activities in the patients leukocytes was negligible. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV001806089 | SCV003523184 | pathogenic | Fucosidosis | 2023-07-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly406*) in the FUCA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 61 amino acid(s) of the FUCA1 protein. This variant is present in population databases (rs764863416, gnomAD 0.0009%). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the FUCA1 protein in which other variant(s) (p.Gln427*) have been determined to be pathogenic (PMID: 8401503). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 975241). This variant is also known as c.1201G>T (p.Gly401*). This premature translational stop signal has been observed in individual(s) with fucosidosis (PMID: 7581404). |
| Centre de Biologie Pathologie Génétique, |
RCV001251771 | SCV001427513 | likely benign | Intellectual disability | 2019-01-01 | no assertion criteria provided | clinical testing |