Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000673096 | SCV000798264 | uncertain significance | Mucopolysaccharidosis, MPS-III-B | 2018-03-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001070181 | SCV001235397 | pathogenic | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease, axonal type 2V | 2019-02-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with leucine at codon 565 of the NAGLU protein (p.Arg565Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs104894598, ExAC 0.006%). This variant has been observed to segregate with mucopolysaccharidosis type III in families (PMID: 23430803). ClinVar contains an entry for this variant (Variation ID: 557013). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg565 amino acid residue in NAGLU. Other variant(s) that disrupt this residue have been observed in individuals with NAGLU-related conditions (PMID: 10094189, 15933803), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |