Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV001578340 | SCV001547964 | uncertain significance | Mucopolysaccharidosis, MPS-IV-A | 2021-02-01 | criteria provided, single submitter | research | Very low frequency in gnomAD v2.1.1 (PM2_moderate) |
Labcorp Genetics |
RCV001578340 | SCV003316021 | uncertain significance | Mucopolysaccharidosis, MPS-IV-A | 2022-04-11 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1048238). This missense change has been observed in individual(s) with mucopolysaccharidosis IVA (PMID: 34387910). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 475 of the GALNS protein (p.His475Asn). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. |
Revvity Omics, |
RCV001578340 | SCV003808574 | uncertain significance | Mucopolysaccharidosis, MPS-IV-A | 2023-12-22 | criteria provided, single submitter | clinical testing |