Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001243859 | SCV001417045 | uncertain significance | Mucopolysaccharidosis type 1 | 2022-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 55 of the IDUA protein (p.Pro55Leu). This variant is present in population databases (rs199554923, gnomAD 0.01%). 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: 968667). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IDUA 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 | RCV002564075 | SCV003721288 | uncertain significance | Inborn genetic diseases | 2024-09-24 | criteria provided, single submitter | clinical testing | The p.P55L variant (also known as c.164C>T), located in coding exon 2 of the IDUA gene, results from a C to T substitution at nucleotide position 164. The proline at codon 55 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
Revvity Omics, |
RCV003132340 | SCV003809964 | uncertain significance | not provided | 2023-05-28 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001243859 | SCV002083086 | uncertain significance | Mucopolysaccharidosis type 1 | 2020-01-17 | no assertion criteria provided | clinical testing | |
Prevention |
RCV004751937 | SCV005364584 | uncertain significance | IDUA-related disorder | 2024-07-10 | no assertion criteria provided | clinical testing | The IDUA c.164C>T variant is predicted to result in the amino acid substitution p.Pro55Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.013% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |