ClinVar Miner

Submissions for variant NM_000263.4(NAGLU):c.700C>T (p.Arg234Cys) (rs104894601)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000001638 SCV000919840 pathogenic Mucopolysaccharidosis, MPS-III-B 2017-11-20 criteria provided, single submitter clinical testing Variant summary: The NAGLU c.700C>T (p.Arg234Cys) variant located in the alpha-n-acetylglucosaminidase, tim-barrel domain (via InterPro) involves the alteration of a conserved nucleotide and 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 10/276804 control chromosomes (gnomAD and publication controls) at a frequency of 0.0000361, which does not exceed the estimated maximal expected allele frequency of a pathogenic NAGLU variant (0.0025). Multiple publications have cited the variant in compound heterozygote and homozygote MPS IIIB pts and found NAGLU activity to be significantly decreased (Mangas_2008). In addition, a reputable database, OMIM classifies the variant as "pathogenic." Taken together, this variant is classified as pathogenic.
Mendelics RCV000001638 SCV001140445 pathogenic Mucopolysaccharidosis, MPS-III-B 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001203422 SCV001374588 pathogenic Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease, axonal type 2V 2020-01-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 234 of the NAGLU protein (p.Arg234Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs104894601, ExAC 0.02%). This variant has been observed in numerous individuals and families affected with NAGLU-related conditions (PMID: 9832037, 30070758, 11286389, 18218046, 23380547). ClinVar contains an entry for this variant (Variation ID: 1572). 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 C1). For these reasons, this variant has been classified as Pathogenic. 5
OMIM RCV000001638 SCV000021794 pathogenic Mucopolysaccharidosis, MPS-III-B 2008-03-01 no assertion criteria provided literature only
Natera, Inc. RCV000001638 SCV001463384 pathogenic Mucopolysaccharidosis, MPS-III-B 2020-09-16 no assertion criteria provided clinical testing

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