Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002017120 | SCV002295622 | uncertain significance | Mucopolysaccharidosis, MPS-IV-A | 2021-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan with arginine at codon 491 of the GALNS protein (p.Trp491Arg). The tryptophan residue is weakly conserved and there is a moderate physicochemical difference between tryptophan and arginine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with GALNS-related conditions. 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 not expected to disrupt GALNS protein function. 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. |
| Ambry Genetics | RCV004616955 | SCV005119821 | uncertain significance | Inborn genetic diseases | 2024-06-18 | criteria provided, single submitter | clinical testing | The c.1471T>C (p.W491R) alteration is located in exon 13 (coding exon 13) of the GALNS gene. This alteration results from a T to C substitution at nucleotide position 1471, causing the tryptophan (W) at amino acid position 491 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |