Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000430851 | SCV000516069 | pathogenic | not provided | 2023-02-23 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24767253, 12180151, 22441121, 33961779, 22789865) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780337 | SCV000917517 | pathogenic | Tay-Sachs disease | 2018-07-09 | criteria provided, single submitter | clinical testing | Variant summary: HEXA c.155C>A (p.Ser52X) 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.187G>T, p.Glu63X and c.1168C>T, p.Gln390X). The variant allele was found at a frequency of 1.2e-05 in 246232 control chromosomes. c.155C>A has been reported in the literature in individuals affected with Tay-Sachs Disease (Gort_2012, McGinniss_2002, Zampieri_2012). At least one patient tested in these studies had <10% enzyme activity reported in the publication. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV000780337 | SCV001211559 | pathogenic | Tay-Sachs disease | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser52*) 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). This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Tay–Sachs disease (PMID: 22441121). ClinVar contains an entry for this variant (Variation ID: 379311). For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV000780337 | SCV002024979 | pathogenic | Tay-Sachs disease | 2019-08-09 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000780337 | SCV002089761 | pathogenic | Tay-Sachs disease | 2017-08-17 | no assertion criteria provided | clinical testing |