Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000079019 | SCV000225229 | pathogenic | not provided | 2014-01-23 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000079019 | SCV000321695 | pathogenic | not provided | 2022-02-07 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15309681, 23401410, 25287660, 15241807, 10814710, 23876334, 15235041, 25137622, 12442278, 26502894, 7795586, 8829629, 24726177, 16287098, 22940367, 30927141, 34426522, 31589614, 34896230, 33636292, 9375852, 9298823, 34504088) |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000000735 | SCV000745324 | likely pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2015-09-21 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000000735 | SCV000831519 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 386 of the GALNS protein (p.Arg386Cys). This variant is present in population databases (rs118204437, gnomAD 0.05%). This missense change has been observed in individuals with Morquio syndrome (PMID: 7795586, 9298823, 22976768, 23227063, 24726177, 26147980). ClinVar contains an entry for this variant (Variation ID: 700). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects GALNS function (PMID: 7795586, 15309681). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781397 | SCV000919394 | pathogenic | Morquio syndrome | 2017-12-04 | criteria provided, single submitter | clinical testing | Variant summary: The GALNS c.1156C>T (p.Arg386Cys) variant involves the alteration of a conserved nucleotide and 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). A functional study, Fukuda_1996, supports these predictions with the observation that the variant causes deficient GALNS activity. This variant was found in 23/275538 control chromosomes (gnomAD) at a frequency of 0.0000835, which does not exceed the estimated maximal expected allele frequency of a pathogenic GALNS variant (0.0020412). Multiple publications have cited the variant in affected homozygous and compound heterozygous pts. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
Baylor Genetics | RCV000000735 | SCV001528502 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2018-03-01 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as pathogenic [PMID 7795586, 8829629, 25287660, 22940367] |
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000000735 | SCV001547906 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2021-02-01 | criteria provided, single submitter | research | De novo (both maternity and paternity confirmed) in a patient with the disease and no family history (PS2_strong); in vitro and in 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_strong); 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); cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1_supporting); multiple lines of computational evidence support a deleterious effect on the gene (PP3_supporting) |
Revvity Omics, |
RCV000000735 | SCV002024160 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2023-06-09 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000000735 | SCV002044999 | likely pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Huiwen Zhang's lab, |
RCV000000735 | SCV004697581 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2022-02-23 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000000735 | SCV000020885 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | 2004-01-01 | no assertion criteria provided | literature only | |
Diagnostic Laboratory, |
RCV000000735 | SCV000733545 | pathogenic | Mucopolysaccharidosis, MPS-IV-A | no assertion criteria provided | clinical testing | ||
Gene |
RCV000000735 | SCV001761899 | not provided | Mucopolysaccharidosis, MPS-IV-A | no assertion provided | literature only |