ClinVar Miner

Submissions for variant NM_000181.4(GUSB):c.1831C>T (p.Arg611Trp)

gnomAD frequency: 0.00001  dbSNP: rs121918176
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000000945 SCV002125034 uncertain significance Mucopolysaccharidosis type 7 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 611 of the GUSB protein (p.Arg611Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs121918176, ExAC 0.001%). This missense change has been observed in individual(s) with mucopolysaccharidosis type VII (PMID: 8111413). ClinVar contains an entry for this variant (Variation ID: 897). 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"). Experimental studies have shown that this missense change affects GUSB function (PMID: 8111413). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000000945 SCV005185834 likely pathogenic Mucopolysaccharidosis type 7 2024-05-14 criteria provided, single submitter clinical testing Variant summary: GUSB c.1831C>T (p.Arg611Trp) results in a non-conservative amino acid change located in the Glycoside hydrolase family 2, catalytic domain (IPR006103) 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 4e-06 in 251484 control chromosomes (gnomAD). c.1831C>T has been reported in the literature in an individuals affected with Mucopolysaccharidosis Type VII (Sly Syndrome; Wu_1993). These data do not allow any conclusion about variant significance. This publication reports experimental evidence evaluating an impact on protein function, finding that the variant results in 0% of normal enzymatic activity. The following publication has been ascertained in the context of this evaluation (PMID: 8111413). ClinVar contains an entry for this variant (Variation ID: 897). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000000945 SCV005674367 likely pathogenic Mucopolysaccharidosis type 7 2024-05-18 criteria provided, single submitter clinical testing
OMIM RCV000000945 SCV000021095 pathogenic Mucopolysaccharidosis type 7 1993-01-01 no assertion criteria provided literature only

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