Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001977478 | SCV002263361 | uncertain significance | Intellectual disability, autosomal dominant 5 | 2023-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1080 of the SYNGAP1 protein (p.Ala1080Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SYNGAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1473274). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SYNGAP1 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Institute of Human Genetics, |
RCV001977478 | SCV003920735 | likely pathogenic | Intellectual disability, autosomal dominant 5 | 2023-05-01 | criteria provided, single submitter | clinical testing | This variant has been identified by standard clinical testing. de novo Selected ACMG criteria: Likely pathogenic (II):PP2;PM2;PS2 |