Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000004140 | SCV002317352 | likely pathogenic | Tay-Sachs disease | 2021-09-28 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly454 amino acid residue in HEXA. Other variant(s) that disrupt this residue have been observed in individuals with HEXA-related conditions (PMID: 9851891, 31388111), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with Tay-Sachs disease (PMID: 16088929). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 454 of the HEXA protein (p.Gly454Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. |
| OMIM | RCV000004140 | SCV000024306 | affects | Tay-Sachs disease | 2021-09-09 | no assertion criteria provided | literature only |