Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004217597 | SCV003731969 | uncertain significance | not specified | 2024-04-29 | criteria provided, single submitter | clinical testing | The c.3737C>T (p.S1246L) alteration is located in exon 29 (coding exon 28) of the ARHGEF10 gene. This alteration results from a C to T substitution at nucleotide position 3737, causing the serine (S) at amino acid position 1246 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Ce |
RCV003434675 | SCV004159417 | likely benign | not provided | 2023-01-01 | criteria provided, single submitter | clinical testing | ARHGEF10: BP4, BS2 |
| Labcorp Genetics |
RCV003434675 | SCV004613304 | uncertain significance | not provided | 2024-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1246 of the ARHGEF10 protein (p.Ser1246Leu). This variant is present in population databases (rs111978809, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ARHGEF10-related conditions. ClinVar contains an entry for this variant (Variation ID: 2384766). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ARHGEF10 protein function with a negative predictive value of 80%. 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. |