Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000004138 | SCV001581385 | pathogenic | Tay-Sachs disease | 2022-10-13 | criteria provided, single submitter | clinical testing | This variant is also known as frameshift codon 142. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 3932). This premature translational stop signal has been observed in individual(s) with Tay-Sachs disease (PMID: 8490625). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe142*) 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). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000004138 | SCV001983501 | pathogenic | Tay-Sachs disease | 2021-09-26 | criteria provided, single submitter | clinical testing | Variant summary: HEXA c.425_426delTT (p.Phe142X) 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 was absent in 251452 control chromosomes. c.425_426delTT has been reported in the literature in individuals affected with Tay-Sachs Disease and has been subsequently cited by others (example Akli_1993). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
OMIM | RCV000004138 | SCV000024304 | affects | Tay-Sachs disease | 1993-01-01 | no assertion criteria provided | literature only | |
Natera, |
RCV000004138 | SCV002089749 | pathogenic | Tay-Sachs disease | 2017-03-16 | no assertion criteria provided | clinical testing |