Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000522695 | SCV000617693 | pathogenic | not provided | 2017-10-20 | criteria provided, single submitter | clinical testing | The R393X variant in the HEXA gene has been reported previously in association with infantile Tay-Sachs disease (Akli et al., 1991; Ozkara et al., 1998; Haghighi et al., 2011). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R393X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret R393X as a pathogenic variant. |
Invitae | RCV000004111 | SCV000955425 | pathogenic | Tay-Sachs disease | 2023-11-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg393*) 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 (rs121907963, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with hexosaminidase A deficiency (PMID: 1837283, 21796138, 24518553, 32968423). ClinVar contains an entry for this variant (Variation ID: 3905). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000004111 | SCV001482257 | pathogenic | Tay-Sachs disease | 2021-02-22 | criteria provided, single submitter | clinical testing | Variant summary: HEXA c.1177C>T (p.Arg393X) 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. The variant allele was found at a frequency of 1.2e-05 in 251470 control chromosomes (gnomAD). c.1177C>T has been reported in the literature in multiple individuals (including several homozygous patients) affected with Tay-Sachs Disease (example: Akli_1991, Jamali_2014, Naseer_2020). These data indicate that the variant is very likely to be associated with disease. Akli et al report that northern blot analysis of fibroblasts derived from a patient homozygous for the variant showed no detectable level of mRNA (Akli_1991). Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Revvity Omics, |
RCV000004111 | SCV002024985 | pathogenic | Tay-Sachs disease | 2019-02-13 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000004111 | SCV000024277 | affects | Tay-Sachs disease | 1991-09-01 | no assertion criteria provided | literature only | |
Counsyl | RCV000004111 | SCV001132224 | likely pathogenic | Tay-Sachs disease | 2015-04-22 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000004111 | SCV002085677 | pathogenic | Tay-Sachs disease | 2017-03-17 | no assertion criteria provided | clinical testing |