Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000490557 | SCV002294936 | likely pathogenic | Multiple sulfatase deficiency | 2023-08-17 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this missense change affects SUMF1 function (PMID: 28566233). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. ClinVar contains an entry for this variant (Variation ID: 225909). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 113 of the SUMF1 protein (p.Glu113Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with multiple sulfatase deficiency (PMID: 28566233). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. |
Gene |
RCV003327381 | SCV004034787 | pathogenic | not provided | 2023-03-08 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect on protein function (Jaszczuk et al., 2017); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21224894, 28566233) |
Children's Hospital DNA Laboratory, |
RCV000490557 | SCV000267645 | pathogenic | Multiple sulfatase deficiency | 2016-04-01 | no assertion criteria provided | case-control |