Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002880698 | SCV003234829 | uncertain significance | Mucopolysaccharidosis, MPS-IV-A | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 380 of the GALNS protein (p.Arg380Lys). This variant also falls at the last nucleotide of exon 10, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GALNS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. This variant disrupts the p.Arg380 amino acid residue in GALNS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15309681, 17876718, 24726177). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. |