Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001865475 | SCV002293941 | uncertain significance | HNSHA due to aldolase A deficiency | 2022-07-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 201 of the ALDOA protein (p.Arg201His). This variant is present in population databases (rs534264493, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ALDOA-related conditions. ClinVar contains an entry for this variant (Variation ID: 423153). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine 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. |
| Gene |
RCV000482537 | SCV000572810 | uncertain significance | not specified | 2017-11-01 | criteria provided, single submitter | clinical testing | The R201H variant in the ALDOA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R201H variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R201H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R201H as a variant of uncertain significance. |