Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV001578473 | SCV001547585 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2021-02-01 | criteria provided, single submitter | research | Splicing variant in canonical site (PVS1_very strong); in vitro and in vivo functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; RNA studies; PS3_strong); the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_strong); absent from gnomAD v2.1.1 (PM2_moderate) |
Labcorp Genetics |
RCV001578473 | SCV003443648 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2023-05-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1048370). This variant is also known as IVS1+1G>A. Disruption of this splice site has been observed in individual(s) with mucopolysaccharidosis type IVA (PMID: 16378744). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 1 of the GALNS gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GALNS are known to be pathogenic (PMID: 12442278). |
Revvity Omics, |
RCV001578473 | SCV004236689 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2023-03-07 | criteria provided, single submitter | clinical testing |