Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Foundation for Research in Genetics and Endocrinology, |
RCV001376071 | SCV001572887 | pathogenic | Hurler syndrome | 2021-02-13 | criteria provided, single submitter | clinical testing | A homozygous 4 base pair deletion in exon 8 of the IDUA gene that results in a frameshift and premature truncation of the protein 73 amino acids downstream to codon 366 was detected. The observed variant c.1096_1099del (p.Thr366Argfster73) has not been reported in the 1000 genomes and ExAC databases. The in silico prediction of the variant is damaging by MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as pathogenic. |
| Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV003448402 | SCV004176689 | likely pathogenic | Mucopolysaccharidosis, MPS-I-H/S | 2023-03-01 | criteria provided, single submitter | clinical testing | The frameshift c.1096_1099del(p.Thr366ArgfsTer73) variant in IDUA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. This variant causes a frameshift starting with codon Threonine 366, changes this amino acid to Arginine residue, and creates a premature Stop codon at position 73 of the new reading frame, denoted p.Thr366ArgfsTer73. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic. In the absence of another reportable variant, the molecular diagnosis is not confirmed. |