Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001322956 | SCV001513853 | uncertain significance | Mucopolysaccharidosis type 1 | 2022-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 448 of the IDUA protein (p.Ala448Asp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with IDUA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1022974). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV003166886 | SCV003879708 | uncertain significance | Inborn genetic diseases | 2023-03-06 | criteria provided, single submitter | clinical testing | The c.1343C>A (p.A448D) alteration is located in exon 9 (coding exon 9) of the IDUA gene. This alteration results from a C to A substitution at nucleotide position 1343, causing the alanine (A) at amino acid position 448 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Natera, |
RCV001322956 | SCV002075356 | uncertain significance | Mucopolysaccharidosis type 1 | 2020-08-18 | no assertion criteria provided | clinical testing |