ClinVar Miner

Submissions for variant NM_000203.5(IDUA):c.1040G>C (p.Ser347Thr)

dbSNP: rs780106243
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001973995 SCV002262810 likely pathogenic Mucopolysaccharidosis type 1 2023-12-09 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 347 of the IDUA protein (p.Ser347Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with a positive newborn screening result for IDUA-related disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 1478034). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IDUA protein function with a positive predictive value of 80%. This variant disrupts the p.Ser347 amino acid residue in IDUA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25102484, 31194252). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Revvity Omics, Revvity RCV003134312 SCV003809951 uncertain significance not provided 2023-05-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003230722 SCV003928845 uncertain significance not specified 2024-04-24 criteria provided, single submitter clinical testing Variant summary: IDUA c.1040G>C (p.Ser347Thr) results in a conservative amino acid change located in the Glycosyl hydrolases family 39, N-terminal catalytic domain (IPR049166) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 248336 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1040G>C in individuals affected with Mucopolysaccharidosis Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1478034). Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV005042636 SCV005667766 likely pathogenic Mucopolysaccharidosis, MPS-I-S; Hurler syndrome; Mucopolysaccharidosis, MPS-I-H/S 2024-05-03 criteria provided, single submitter clinical testing

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