ClinVar Miner

Submissions for variant NM_000202.8(IDS):c.253G>A (p.Ala85Thr) (rs113993949)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000790731 SCV000228820 pathogenic not provided 2012-09-05 criteria provided, single submitter clinical testing
LISIN Facultad de Ciencias Exactas, Universidad Nacional de La Plata RCV000177016 SCV000262519 pathogenic Mucopolysaccharidosis, MPS-II 2007-05-16 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000177016 SCV000919530 pathogenic Mucopolysaccharidosis, MPS-II 2018-08-17 criteria provided, single submitter clinical testing Variant summary: IDS c.253G>A (p.Ala85Thr) results in a non-conservative amino acid change located in the Sulfatase, N-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 169233 control chromosomes (gnomAD). c.253G>A has been reported in the literature in multiple individuals affected with Mucopolysaccharidosis Type II (Hunter Syndrome)(Alkhzouz_2016, Amartino_2014, Dvorakova_2017, Kosuga_2016). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Alkhzouz_2016). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences RCV000177016 SCV001479333 pathogenic Mucopolysaccharidosis, MPS-II criteria provided, single submitter clinical testing
Pediatrics,All India Institute of Medical Sciences, New Delhi RCV000177016 SCV001573770 affects Mucopolysaccharidosis, MPS-II 2014-04-01 no assertion criteria provided research The change c.253G>A, (p.A85T) was found to be a known missense variant, where the non-polar amino acid Alanine at 85 position was substituted with another polar amino acid Threonine. Uttarilli et al., described it in MPS II patients with attenuated phenotype from Kerala and Karnataka (Uttarilli et al.,2016). Rathmann et al., described A85T initially in one European MPS-II patients with attenuated phenotype (Rathmann et al.,1982). In our study, it was detected in the hemizygous condition in patients with MPS-II attenuated phenotype, hails from from the state of UP and Bihar, India.

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