Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000409594 | SCV000487266 | pathogenic | Mucopolysaccharidosis, MPS-III-B | 2016-11-04 | criteria provided, single submitter | clinical testing | |
| Centre for Mendelian Genomics, |
RCV000626636 | SCV000747338 | pathogenic | Hypertrichosis; Abnormality of metabolism/homeostasis; Coarse facial features; Abnormal facial shape; Thick eyebrow; Hepatosplenomegaly; Mucopolysacchariduria; Intellectual disability, severe | 2017-01-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000705481 | SCV000834480 | pathogenic | Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease, axonal type 2V | 2018-05-15 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 140 of the NAGLU protein (p.Tyr140Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs753520553, ExAC 0.009%). This variant has been reported to co-occur with different NAGLU variants or as homozygous in multiple individuals affected with mucopolysaccharidosis IIIB (PMID: 9950362, 9443875, 26907177, 9443878, 11153910). It has also been reported in families with evidence of co-segregation with disease (PMID: 14984474). ClinVar contains an entry for this variant (Variation ID: 371634). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic. |
| Integrated Genetics/Laboratory Corporation of America | RCV000409594 | SCV000919842 | pathogenic | Mucopolysaccharidosis, MPS-III-B | 2018-07-06 | criteria provided, single submitter | clinical testing | Variant summary: NAGLU c.419A>G (p.Tyr140Cys) results in a non-conservative amino acid change located in the Alpha-N-acetylglucosaminidase, tim-barrel domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 246256 control chromosomes (gnomAD). The variant, c.419A>G, has been reported in the literature in multiple compound heterozygote and homozygote individuals affected with Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B)(Beesley_1998, Bunge_1998, Meijer_2016, Tessitore_2000). These data indicate that the variant is very likely to be associated with disease. The affected patients were found to have significantly decreased enzyme activity (<10%)(Beesley_1998). Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic. |
| Laboratory of Diagnosis and Therapy of Lysosomal Disorders, |
RCV000409594 | SCV000929906 | likely pathogenic | Mucopolysaccharidosis, MPS-III-B | 2019-01-01 | criteria provided, single submitter | literature only | PS3: Low in vitro enzymatic activity. PM2: Very low frequency in ExAC |