Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics, |
RCV003994645 | SCV004812403 | uncertain significance | Charlevoix-Saguenay spastic ataxia | 2022-12-23 | criteria provided, single submitter | clinical testing | This sequence change in SACS is a frameshift variant predicted to cause a premature stop codon, p.(Asn4521*), that is predicted to escape nonsense-mediated decay and remove <10% of the protein, however it is a truncation of a functionally important HEPN domain (removes amino acids 4521-4579) in a gene where loss of function is an established disease mechanism (PMID: 21507954). This variant is absent from the population database gnomAD v2.1 and v3.1. To our knowledge, this variant has not been reported in the relevant scientific literature or databases. Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PVS1_Strong, PM2_Supporting. |