Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001926683 | SCV002204628 | uncertain significance | Multiple sulfatase deficiency | 2022-08-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 345 of the SUMF1 protein (p.Arg345His). This variant is present in population databases (rs139267495, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SUMF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1425494). 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. |
| Gene |
RCV003159221 | SCV003852977 | likely pathogenic | not provided | 2023-03-31 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV004970552 | SCV005511317 | likely pathogenic | Inborn genetic diseases | 2024-09-19 | criteria provided, single submitter | clinical testing | The c.1034G>A (p.R345H) alteration is located in exon 9 (coding exon 9) of the SUMF1 gene. This alteration results from a G to A substitution at nucleotide position 1034, causing the arginine (R) at amino acid position 345 to be replaced by a histidine (H). Based on data from gnomAD, the A allele has an overall frequency of 0.001% (3/248908) total alleles studied. The highest observed frequency was 0.006% (1/16256) of African alleles. This variant has been identified in the homozygous state and/or in conjunction with other SUMF1 variant(s) in individual(s) with features consistent with multiple sulfatase deficiency; in at least one instance, the variants were identified in trans (Adang, 2020). This amino acid position is highly conserved in available vertebrate species. In an assay testing SUMF1 function, this variant showed a functionally abnormal result (Adang, 2020). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |