Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000331371 | SCV000399629 | uncertain significance | Morquio syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | The c.1247T>C (p.Ile416Thr) variant has been identified in a homozygous state in one individual diagnosed with mucopolysaccharidosis, type IVA (Morrone et al. 2014). Control data are unavailable for this variant, which is reported at a frequency of 0.00175 in the European American population of the Exome Sequencing Project. The evidence for this variant is limited. The p.Ile416Thr variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for mucopolysaccharidosis, type IV. |
Labcorp Genetics |
RCV000894656 | SCV001038655 | likely benign | Mucopolysaccharidosis, MPS-IV-A | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000894656 | SCV001547940 | uncertain significance | Mucopolysaccharidosis, MPS-IV-A | 2021-02-01 | criteria provided, single submitter | curation | In vivo functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; PS3_supporting) |
Genome- |
RCV000894656 | SCV002044937 | likely benign | Mucopolysaccharidosis, MPS-IV-A | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235192 | SCV003934590 | uncertain significance | not specified | 2023-05-09 | criteria provided, single submitter | clinical testing | Variant summary: GALNS c.1247T>C (p.Ile416Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00092 in 249798 control chromosomes in the gnomAD database, including 3 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in GALNS causing Mucopolysaccharidosis Type IVA (Morquio Syndrome A) (0.00092 vs 0.002), allowing no conclusion about variant significance. c.1247T>C has been reported in the literature in a homozygous individual affected with Mucopolysaccharidosis Type IVA (Morquio Syndrome A) (Morrone_2014). These data indicate that the variant could be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 24726177, 29140481). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments classifying the variant as uncertain significance (n=2) or likely benign (n=2). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Mayo Clinic Laboratories, |
RCV003480600 | SCV004224273 | uncertain significance | not provided | 2023-02-07 | criteria provided, single submitter | clinical testing |