Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000175552 | SCV000227058 | likely benign | not specified | 2014-06-19 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000664739 | SCV000788747 | uncertain significance | Hurler syndrome | 2017-01-06 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000779453 | SCV000916078 | uncertain significance | Mucopolysaccharidosis type 1 | 2018-08-30 | criteria provided, single submitter | clinical testing | The IDUA c.245A>C (p.His82Pro) missense variant has been reported in two studies and is found in two individuals in a compound heterozygous state (Clarke and Scott 1993; Venturi et al. 2002). These individuals exhibited an intermediate phenotype characteristic of the Hurler-Scheie syndrome form of mucopolysaccharidosis, type I (MPS I), and also carried a known pathogenic stop-gained variant. The p.His82Pro variant was also reported in a heterozygous state in two additional patients with MPS I in whom a second variant was not identified. The variant was not found in 168 tested control chromosomes. The p.His82Pro variant is reported at a frequency of 0.000017 in the European (non-Finnish) population of the Genome Aggregation Database, though this is based on two alleles in a region of good sequence coverage so the variant is presumed to be rare. Based on the limited evidence, p.His82Pro is classified as a variant is of unknown significance but suspicious for pathogenicity for mucopolysaccharidosis, type I. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Mendelics | RCV000664739 | SCV001136674 | benign | Hurler syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000779453 | SCV001420326 | uncertain significance | Mucopolysaccharidosis type 1 | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 82 of the IDUA protein (p.His82Pro). This variant is present in population databases (rs794727239, gnomAD 0.002%). This missense change has been observed in individual(s) with MPS I (PMID: 8401515). ClinVar contains an entry for this variant (Variation ID: 195039). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
Revvity Omics, |
RCV003129795 | SCV003817577 | uncertain significance | not provided | 2023-03-19 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000779453 | SCV002083090 | uncertain significance | Mucopolysaccharidosis type 1 | 2020-06-10 | no assertion criteria provided | clinical testing |