Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000806517 | SCV000946521 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2023-04-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg94 amino acid residue in GALNS. Other variant(s) that disrupt this residue have been observed in individuals with GALNS-related conditions (PMID: 7795586, 9298823, 10814710, 23876334, 29731656), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects GALNS function (PMID: 7795586, 10814710). 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) performed at Invitae indicates that this missense variant is expected to disrupt GALNS protein function. ClinVar contains an entry for this variant (Variation ID: 651205). This missense change has been observed in individuals with mucopolysaccharidosis type IVa (PMID: 10814710, 23876334, 29731656). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 94 of the GALNS protein (p.Arg94Cys). |
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000806517 | SCV001547646 | likely pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2021-02-01 | criteria provided, single submitter | research | In vitro and vivo functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; low to null in vitro enzymatic activity; PS3_moderate); the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_strong); very low frequency in gnomAD v2.1.1 (PM2_moderate); multiple lines of computational evidence support a deleterious effect on the gene (PP3_supporting) |
Revvity Omics, |
RCV000806517 | SCV002024159 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2021-09-16 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000806517 | SCV002045034 | likely pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000806517 | SCV002803365 | likely pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2024-05-07 | criteria provided, single submitter | clinical testing |