Submissions for variant NM_000046.5(ARSB):c.962T>C (p.Leu321Pro)

dbSNP: rs1554079320

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV000677614	SCV000803132	pathogenic	Mucopolysaccharidosis type 6	2018-01-01	criteria provided, single submitter	curation	In vitro functional studies supportive of a damaging effect on the gene product (low to no ARSB activity in homozygotes; PS3); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1-strong evidence); Absent from GnomAD (PM2)
CeGaT Center for Human Genetics Tuebingen	RCV001796768	SCV002563838	pathogenic	not provided	2020-11-01	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV000677614	SCV002768561	pathogenic	Mucopolysaccharidosis type 6	2020-05-21	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.1.0, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from leucine to proline. (N) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0502 - Missense variant with conflicting in-silico predictions and/or uninformative conservation. (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0801 - Strong previous evidence of pathogenicity in unrelated individuals. (ClinVar, LOVD, Tomanin, R. et al. (2018)) (P) 0903 - Low evidence for segregation with disease. (Zanetti, A. et al . (2014)) (P) 1001 - Strong functional evidence supporting abnormal protein function. (Zanetti, A. et al . (2014)) (P)
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001796768	SCV002037296	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001796768	SCV002037990	pathogenic	not provided		no assertion criteria provided	clinical testing