Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000657915 | SCV000779682 | likely pathogenic | not provided | 2018-05-16 | criteria provided, single submitter | clinical testing | A likely pathogenic variant has been identified in the SGSH gene. The T321A variant has been reported previously in the homozygous state in an individual with mucopolysaccharidosis type IIIA; however, it is not known whether biparental inheritance was confirmed (Bunge et al., 1997). The T321A variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The T321A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Additionally, missense variants in nearby residues have been reported in the Human Gene Mutation Database in individuals with mucopolysaccharidosis type IIIA (Stenson et al., 2014). Based on the currently available information, we interpret T321A as a likely pathogenic variant. |
| Counsyl | RCV000667635 | SCV000792115 | uncertain significance | Mucopolysaccharidosis, MPS-III-A | 2017-06-21 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV000667635 | SCV002045092 | likely pathogenic | Mucopolysaccharidosis, MPS-III-A | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000667635 | SCV003287132 | uncertain significance | Mucopolysaccharidosis, MPS-III-A | 2022-07-12 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 321 of the SGSH protein (p.Thr321Ala). This variant is present in population databases (rs758756630, gnomAD 0.0009%). This missense change has been observed in individual(s) with mucopolysaccharidosis type III (PMID: 9401012). ClinVar contains an entry for this variant (Variation ID: 546107). 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"). 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. |