Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000671547 | SCV000796532 | likely pathogenic | Sandhoff disease | 2017-12-28 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000671547 | SCV001363963 | pathogenic | Sandhoff disease | 2019-01-10 | criteria provided, single submitter | clinical testing | Variant summary: HEXB c.146C>A (p.Ser49X) 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. A truncation downstream of this position has been classified as pathogenic by our laboratory (eg. c.850C>T (p.Arg284X)). The variant was absent in 204176 control chromosomes (gnomAD). c.146C>A has been reported in the literature in one homozygous individual affected with Sandhoff Disease while, experimental evidence evaluating an impact on protein function demostrated a residual enzymatic activity of 1.6% compared to normal control (Zampieri_2012). A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV000671547 | SCV001579759 | pathogenic | Sandhoff disease | 2020-04-26 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in HEXB are known to be pathogenic (PMID: 7550345, 18758829). This variant has been observed in individual(s) with Sandhoff disease (PMID: 22848519). ClinVar contains an entry for this variant (Variation ID: 555683). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser49*) in the HEXB gene. It is expected to result in an absent or disrupted protein product. |