ClinVar Miner

Submissions for variant NM_000199.5(SGSH):c.1027dup (p.Leu343fs) (rs778700037)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000478433 SCV000232479 pathogenic not provided 2014-06-03 criteria provided, single submitter clinical testing
GeneDx RCV000478433 SCV000568750 pathogenic not provided 2017-01-16 criteria provided, single submitter clinical testing The c.1027dupC pathogenic variant in the SGSH gene has been reported previously in association with mucopolysaccharidosis IIIA (MPS IIIA) (Weber et al., 1997; Pollard et al., 2013). The duplication causes a frameshift starting with codon Leucine 343, changes this amino acid to a Proline residue and creates a premature Stop codon at position 159 of the new reading frame, denoted p.Leu343ProfsX159. This pathogenic variant is predicted to cause loss of normal protein function through protein truncation.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586132 SCV000695955 pathogenic Sanfilippo syndrome 2017-02-02 criteria provided, single submitter clinical testing Variant summary: The SGSH c.1027dupC (p.Leu343Profs) variant results in a premature termination codon, predicted to cause a truncated or absent SGSH protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 7/118674 control chromosomes at a frequency of 0.000059, which does not exceed the estimated maximal expected allele frequency of a pathogenic SGSH variant (0.0032275). This variant has been reported in multiple affected individuals as compund heterozygotes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000180105 SCV001233391 pathogenic Mucopolysaccharidosis, MPS-III-A 2020-09-08 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SGSH gene (p.Leu343Profs*159). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 160 amino acids of the SGSH protein. This variant is present in population databases (rs778700037, ExAC 0.01%). This variant has been observed in individual(s) with mucopolysaccharidosis type III (PMID: 15146460, 21204211, 24314109). This variant is also known as c.1026dupC, c.1027_1028insC, and insC1039 in the literature. ClinVar contains an entry for this variant (Variation ID: 198694). Experimental studies have shown that this variant affects SGSH protein function (PMID: 15146460). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001266816 SCV001444995 pathogenic Inborn genetic diseases 2019-12-09 criteria provided, single submitter clinical testing
Counsyl RCV000180105 SCV000486596 pathogenic Mucopolysaccharidosis, MPS-III-A 2016-11-03 no assertion criteria provided clinical testing
Natera, Inc. RCV000180105 SCV001463875 pathogenic Mucopolysaccharidosis, MPS-III-A 2020-09-16 no assertion criteria provided clinical testing

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