Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute for Clinical Genetics, |
RCV003238068 | SCV002009520 | likely pathogenic | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003772104 | SCV004633016 | likely pathogenic | Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders | 2023-02-21 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Arg420 amino acid residue in SYN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 420 of the SYN1 protein (p.Arg420Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SYN1-related conditions (PMID: 31969655). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1319815). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Studies have shown that this missense change alters SYN1 gene expression (PMID: 31969655). 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. |
OMIM | RCV001762014 | SCV002583586 | pathogenic | Intellectual disability, X-linked 50 | 2022-10-14 | no assertion criteria provided | literature only |