Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000690590 | SCV000818280 | uncertain significance | Mucopolysaccharidosis, MPS-III-A | 2022-07-26 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 486 of the SGSH protein (p.Val486Ile). This variant is present in population databases (rs764585957, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SGSH-related conditions. ClinVar contains an entry for this variant (Variation ID: 569858). 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: "Benign"; Align-GVGD: "Class C25"). This variant disrupts the p.Val486 amino acid residue in SGSH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11182930). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
Genome- |
RCV000690590 | SCV002045118 | uncertain significance | Mucopolysaccharidosis, MPS-III-A | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002544881 | SCV003526630 | uncertain significance | Inborn genetic diseases | 2021-08-16 | criteria provided, single submitter | clinical testing | The c.1456G>A (p.V486I) alteration is located in exon 8 (coding exon 8) of the SGSH gene. This alteration results from a G to A substitution at nucleotide position 1456, causing the valine (V) at amino acid position 486 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV000690590 | SCV001455447 | uncertain significance | Mucopolysaccharidosis, MPS-III-A | 2019-11-11 | no assertion criteria provided | clinical testing |