Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000004117 | SCV000917514 | pathogenic | Tay-Sachs disease | 2018-06-04 | criteria provided, single submitter | clinical testing | Variant summary: HEXA c.78G>A (p.Trp26X) 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 (eg. c.1168C>T, p.Gln390X; c.1274_1277dupTATC, p.Tyr427fsX5). The variant was absent in 121186 control chromosomes. c.78G>A has been reported in the literature in individuals affected with Tay-Sachs Disease. These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. 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. |
Invitae | RCV000004117 | SCV001586702 | pathogenic | Tay-Sachs disease | 2022-10-31 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 3911). This premature translational stop signal has been observed in individual(s) with Tay-Sachs disease (PMID: 1833974, 21967858, 25606403). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp26*) in the HEXA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HEXA are known to be pathogenic (PMID: 1833974, 8490625). |
OMIM | RCV000004117 | SCV000024283 | affects | Tay-Sachs disease | 1993-01-01 | no assertion criteria provided | literature only | |
Natera, |
RCV000004117 | SCV002089763 | pathogenic | Tay-Sachs disease | 2017-03-17 | no assertion criteria provided | clinical testing |