ClinVar Miner

Submissions for variant NM_182760.4(SUMF1):c.1033C>T (p.Arg345Cys)

gnomAD frequency: 0.00001  dbSNP: rs137852852
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000002794 SCV002123479 pathogenic Multiple sulfatase deficiency 2023-12-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 345 of the SUMF1 protein (p.Arg345Cys). This variant is present in population databases (rs137852852, gnomAD 0.01%). This missense change has been observed in individual(s) with multiple sulfatase deficiency (PMID: 12757706, 21224894). ClinVar contains an entry for this variant (Variation ID: 2675). 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%. Experimental studies have shown that this missense change affects SUMF1 function (PMID: 21224894). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000002794 SCV002807235 pathogenic Multiple sulfatase deficiency 2021-11-11 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000002794 SCV004175833 pathogenic Multiple sulfatase deficiency 2023-02-14 criteria provided, single submitter clinical testing The missense c.1033C>T(p.Arg345Cys) variant in SUMF1 gene has been reported in homozygous state in multiple individual affected with multiple sulfatase deficiency (Schlotawa L, et. al., 2011; Cosma MP, et. al., 2003). Experimental studies have shown disruption of protein (Schlotawa L, et. al., 2011). The variant is reported with an allele frequency of 0.0004% in the gnomAD exomes database and is novel (not in any individuals) in 1000 Genomes database. This variant has been reported to the ClinVar database as Pathogenic. The amino acid change p.Arg345Cys in SUMF1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Arg at position 345 is changed to a Cys changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000002794 SCV000022952 pathogenic Multiple sulfatase deficiency 2011-03-01 no assertion criteria provided literature only
GeneReviews RCV000002794 SCV000899284 not provided Multiple sulfatase deficiency no assertion provided literature only

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