ClinVar Miner

Submissions for variant NM_000199.5(SGSH):c.265_269del (p.Tyr89fs)

dbSNP: rs2041840084
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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 RCV001193148 SCV001361817 pathogenic Mucopolysaccharidosis, MPS-III-A 2023-08-01 criteria provided, single submitter clinical testing Variant summary: SGSH c.265_269delTACGG (p.Tyr89AlafsX45) 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 248634 control chromosomes (gnomAD). c.265_269delTACGG has been reported in the literature in at least one biallelic individual affected with Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome A) (Pollard_2013). 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. The following publication has been ascertained in the context of this evaluation (PMID: 22976768). One ClinVar submitter has assessed the variant since 2014, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001193148 SCV002235077 pathogenic Mucopolysaccharidosis, MPS-III-A 2022-12-30 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 928757). This sequence change creates a premature translational stop signal (p.Tyr89Alafs*45) in the SGSH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SGSH are known to be pathogenic (PMID: 11182930, 21204211, 22976768). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of Sanfilippo syndrome A (PMID: 22976768).

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