Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000211105 | SCV000268074 | likely pathogenic | Intellectual disability, autosomal dominant 5 | 2015-01-01 | criteria provided, single submitter | literature only | |
Labcorp Genetics |
RCV000211105 | SCV004268343 | uncertain significance | Intellectual disability, autosomal dominant 5 | 2023-07-30 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this missense change affects SYNGAP1 function (PMID: 33308442). 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. ClinVar contains an entry for this variant (Variation ID: 225899). This missense change has been observed in individual(s) with intellectual disability (PMID: 27159028). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1165 of the SYNGAP1 protein (p.Ser1165Leu). |