ClinVar Miner

Submissions for variant NM_000199.5(SGSH):c.1153del (p.Arg385fs)

dbSNP: rs2041615714
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001174996 SCV001338492 likely pathogenic Mucopolysaccharidosis, MPS-III-A 2020-04-02 criteria provided, single submitter clinical testing Variant summary: SGSH c.1153delC (p.Arg385AlafsX28) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251050 control chromosomes (gnomAD). c.1153delC has been reported in the literature in at least one individual affected with Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome A- Yogalingam_2001). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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 likely pathogenic.
Invitae RCV001174996 SCV003442421 pathogenic Mucopolysaccharidosis, MPS-III-A 2024-01-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg385Alafs*28) in the SGSH gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 118 amino acid(s) of the SGSH protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type III (PMID: 11668611). This variant is also known as c.1152del. ClinVar contains an entry for this variant (Variation ID: 917772). This variant disrupts a region of the SGSH protein in which other variant(s) (p.Trp479*) have been determined to be pathogenic (PMID: 21204211). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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