Submissions for variant NM_000203.5(IDUA):c.1907_1917del (p.Val636fs)

dbSNP: rs1715314710

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001251348	SCV001426916	likely pathogenic	Mucopolysaccharidosis type 1	2020-07-16	criteria provided, single submitter	clinical testing	Variant summary: IDUA c.1907_1917del11 (p.Val636GlyfsX19) causes a frameshift which results in an extension of the protein. The variant was absent in 249106 control chromosomes. c.1907_1917del11 has been reported in the literature in at least one individual affected with Mucopolysaccharidosis Type 1 (Bunge_1995). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001251348	SCV003520575	uncertain significance	Mucopolysaccharidosis type 1	2022-09-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val636Glyfs*19) in the IDUA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 18 amino acid(s) of the IDUA 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 I (PMID: 7550242). ClinVar contains an entry for this variant (Variation ID: 974984). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.