Submissions for variant NM_182760.4(SUMF1):c.785A>G (p.Gln262Arg)

dbSNP: rs1064793391

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000481019	SCV000565997	likely pathogenic	not provided	2022-06-17	criteria provided, single submitter	clinical testing	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: 30124108, 28720891, 31130284, 28454995)
Ambry Genetics	RCV000624193	SCV000742689	uncertain significance	Inborn genetic diseases	2017-08-15	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: NEGATIVE - No Relevant Alterations Detected (Step 2)
Baylor Genetics	RCV000723283	SCV001522292	pathogenic	Multiple sulfatase deficiency	2020-04-14	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae	RCV000723283	SCV001591305	pathogenic	Multiple sulfatase deficiency	2023-10-28	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 262 of the SUMF1 protein (p.Gln262Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with multiple sulfatase deficiency (PMID: 28454995, 30124108). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 418724). 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 not expected to disrupt SUMF1 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV000723283	SCV002027601	pathogenic	Multiple sulfatase deficiency	2021-09-05	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV004527375	SCV005038888	uncertain significance	Spinocerebellar ataxia type 15/16	2024-03-14	criteria provided, single submitter	clinical testing
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000723283	SCV000854672	pathogenic	Multiple sulfatase deficiency	2018-05-03	no assertion criteria provided	clinical testing