Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001008201 | SCV001167967 | likely pathogenic | not provided | 2018-06-14 | criteria provided, single submitter | clinical testing | The c.1142_1146delTAAAG variant in the HEXA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1142_1146delTAAAG variant causes a frameshift starting with codon Valine 381, changes this amino acid to an Aspartic Acid residue, and creates a premature Stop codon at position 48 of the new reading frame, denoted p.Val381AspfsX48. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1142_1146delTAAAG variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1142_1146delTAAAG as a likely pathogenic variant. |
Invitae | RCV001860588 | SCV002228798 | pathogenic | Tay-Sachs disease | 2022-07-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 817101). This variant has not been reported in the literature in individuals affected with HEXA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val381Aspfs*48) 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). |