Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001362987 | SCV001559056 | uncertain significance | Intellectual disability, autosomal dominant 5 | 2024-03-29 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 699 of the SYNGAP1 protein (p.Val699Met). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 1054479). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SYNGAP1 protein function. 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. |
| Ambry Genetics | RCV004036856 | SCV004961441 | uncertain significance | Inborn genetic diseases | 2024-01-03 | criteria provided, single submitter | clinical testing | The c.2095G>A (p.V699M) alteration is located in exon 12 (coding exon 12) of the SYNGAP1 gene. This alteration results from a G to A substitution at nucleotide position 2095, causing the valine (V) at amino acid position 699 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |