ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.100CTGCTC[1] (p.Leu36_Leu37del)

dbSNP: rs794726887
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000173142 SCV000224231 likely pathogenic not provided 2014-10-10 criteria provided, single submitter clinical testing
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV001578356 SCV001547579 uncertain significance Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter research The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_moderate); absent from gnomAD v2.1.1 (PM2_moderate); protein length changes as a result of in-frame deletions/insertions in a nonrepeat region (PM4_supporting)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003330532 SCV004038483 pathogenic Morquio syndrome 2023-08-09 criteria provided, single submitter clinical testing Variant summary: GALNS c.106_111delCTGCTC (p.Leu36_Leu37del) results in an in-frame deletion that is predicted to remove two amino acids from the encoded protein. The variant was absent in 149554 control chromosomes. c.106_111delCTGCTC has been reported in the literature as a compound heterozygous genotype in multiple individuals affected with Mucopolysaccharidosis Type IVA (Morquio Syndrome A)(example, Yang_2001, Hu_2018, Leong_2019). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 36077388, 29095814, 31200731, 20574428, 11524742, 35212421). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001578356 SCV004316504 pathogenic Mucopolysaccharidosis, MPS-IV-A 2024-01-31 criteria provided, single submitter clinical testing This variant, c.106_111del, results in the deletion of 2 amino acid(s) of the GALNS protein (p.Leu36_Leu37del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with mucopolysaccharidosis type IVA (PMID: 11524742, 31200731). ClinVar contains an entry for this variant (Variation ID: 193104). This variant disrupts a region of the GALNS protein in which other variant(s) (p.Leu36Arg) have been determined to be pathogenic (PMID: 24726177, 25252036; Invitae). 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.
Fulgent Genetics, Fulgent Genetics RCV001578356 SCV005641518 pathogenic Mucopolysaccharidosis, MPS-IV-A 2024-03-05 criteria provided, single submitter clinical testing

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