Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001976685 | SCV002258734 | uncertain significance | not provided | 2021-10-11 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with methionine at codon 1228 of the ARFGEF2 protein (p.Val1228Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs775296325, ExAC 0.04%). This variant has not been reported in the literature in individuals affected with ARFGEF2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV002573507 | SCV003677286 | uncertain significance | Inborn genetic diseases | 2022-04-25 | criteria provided, single submitter | clinical testing | The c.3682G>A (p.V1228M) alteration is located in exon 27 (coding exon 27) of the ARFGEF2 gene. This alteration results from a G to A substitution at nucleotide position 3682, causing the valine (V) at amino acid position 1228 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |