ClinVar Miner

Submissions for variant NM_000199.5(SGSH):c.1105G>A (p.Glu369Lys) (rs104894640)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins NTD, LLC RCV000078349 SCV000232480 pathogenic not provided 2013-08-06 criteria provided, single submitter clinical testing
GeneDx RCV000078349 SCV000582578 pathogenic not provided 2015-09-03 criteria provided, single submitter clinical testing The E369K variant in the SGSH gene has been reported previously in association with mucopolysaccharidosis IIIA (MPS IIIA) (Di Natale et al., 1998; Weber et al., 1997). Two individuals who were compound heterozygous for E369K and a different variant were reported to have a mild-intermediate phenotype (Di Natale et al., 1998; Esposito et al., 2000). In comparison with the wild type, E369K yielded similar molecular size and stability on western blot with the authors predicting the variant does not cause a dramatic change to the protein structure and function (Esposito et al., 2000). Therefore, we interpret E369K as a pathogenic variant.
Counsyl RCV000005424 SCV000790783 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2017-05-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000005424 SCV002015101 pathogenic Mucopolysaccharidosis, MPS-III-A 2021-10-28 criteria provided, single submitter clinical testing Variant summary: SGSH c.1105G>A (p.Glu369Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250408 control chromosomes (gnomAD). c.1105G>A has been reported in the literature in multiple individuals affected with Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome A) (e.g. Di Natale_1998, Esposito_2000, Valstar_2010, Heron_2011). These data indicate that the variant is very likely to be associated with disease. Experimental evidence demonstrated the variant considerably decreases or abolishes enzyme activity (Esposito_2000, Heron_2011). Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Nilou-Genome Lab RCV000005424 SCV002045489 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2021-11-07 criteria provided, single submitter clinical testing
OMIM RCV000005424 SCV000025606 pathogenic Mucopolysaccharidosis, MPS-III-A 2003-04-01 no assertion criteria provided literature only
Human Genetics - Radboudumc,Radboudumc RCV000078349 SCV002037374 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000078349 SCV002037805 pathogenic not provided no assertion criteria provided clinical testing

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