Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000002795 | SCV003525034 | pathogenic | Multiple sulfatase deficiency | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 348 of the SUMF1 protein (p.Ala348Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of multiple sulfatase deficiency (PMID: 12757706). ClinVar contains an entry for this variant (Variation ID: 2676). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SUMF1 protein function with a positive predictive value of 80%. This variant disrupts the p.Ala348 amino acid residue in SUMF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 32048457). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000002795 | SCV000022953 | pathogenic | Multiple sulfatase deficiency | 2003-05-16 | no assertion criteria provided | literature only |