Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
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, |
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, |
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 |