Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002378667 | SCV002684196 | uncertain significance | Cardiovascular phenotype | 2022-07-06 | criteria provided, single submitter | clinical testing | The p.A304T variant (also known as c.910G>A), located in coding exon 3 of the SHOC2 gene, results from a G to A substitution at nucleotide position 910. The alanine at codon 304 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003655376 | SCV004513247 | uncertain significance | RASopathy | 2023-06-04 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs150902461, gnomAD 0.008%). 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. 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 SHOC2 protein function. ClinVar contains an entry for this variant (Variation ID: 1765838). This variant has not been reported in the literature in individuals affected with SHOC2-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 304 of the SHOC2 protein (p.Ala304Thr). |