Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000790540 | SCV000929872 | likely pathogenic | Mucopolysaccharidosis type 1 | 2019-01-01 | criteria provided, single submitter | literature only | PS3: Low in vivo enzymatic activity in homozygote; low in vitro enzymatic activity. PM2: Very low frequency in ExAC. PP3: Multiple lines of computational evidence evidence supporting a deleterious effect |
Labcorp Genetics |
RCV000790540 | SCV001590399 | pathogenic | Mucopolysaccharidosis type 1 | 2023-06-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies have shown that this missense change affects IDUA function (PMID: 15300847). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 638074). This missense change has been observed in individual(s) with Scheie or Hurler-Scheie syndrome, the attenuated forms of mucopolysaccharidosis type I (PMID: 15300847, 21394825, 31194252). This variant is present in population databases (rs369090960, gnomAD 0.001%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 265 of the IDUA protein (p.Gly265Arg). It affects a nucleotide within the consensus splice site. |
Revvity Omics, |
RCV001784404 | SCV002016685 | likely pathogenic | not provided | 2021-09-21 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000790540 | SCV002075316 | pathogenic | Mucopolysaccharidosis type 1 | 2021-09-29 | no assertion criteria provided | clinical testing |