Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001245922 | SCV001419246 | uncertain significance | Combined malonic and methylmalonic acidemia | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with lysine at codon 84 of the ACSF3 protein (p.Arg84Lys). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and lysine. This variant is present in population databases (rs373476048, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with ACSF3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 | RCV002564098 | SCV003756824 | uncertain significance | Inborn genetic diseases | 2021-07-20 | criteria provided, single submitter | clinical testing | The c.251G>A (p.R84K) alteration is located in exon 3 (coding exon 1) of the ACSF3 gene. This alteration results from a G to A substitution at nucleotide position 251, causing the arginine (R) at amino acid position 84 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Natera, |
RCV001245922 | SCV002089498 | uncertain significance | Combined malonic and methylmalonic acidemia | 2021-09-28 | no assertion criteria provided | clinical testing |