Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002013360 | SCV002295804 | uncertain significance | not provided | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 200 of the VPS33A protein (p.Arg200Pro). This variant is present in population databases (rs200032973, gnomAD 0.0009%). This missense change has been observed in individual(s) with mucopolysaccharidosis-plus syndrome (PMID: 36153662). ClinVar contains an entry for this variant (Variation ID: 1500222). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Molecular Genetics Laboratory, |
RCV002284227 | SCV002573590 | likely pathogenic | Mucopolysaccharidosis-plus syndrome | 2022-09-19 | no assertion criteria provided | clinical testing | Whole Exome sequencing (WES) was performed for the patient, the WES analysis revealed a homozygous variant in VPS33A (NM_022916.4): c.599G>C: p.Arg200Pro. This variant is very rare, was reported in gnomAD only in one heterozygous carrier, it is fully conserved amongst different species and predicted deleterious in in silico prediction tools. The variant was validated by Sanger sequencing performed at our clinical lab. Familial segregation showed that both parents are heterozygous carriers, healthy brother and sister were also heterozygous carriers |