Submissions for variant NM_000203.5(IDUA):c.1118A>C (p.Asn373Thr)

gnomAD frequency: 0.00057  dbSNP: rs140564189

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000412931	SCV000492075	uncertain significance	not specified	2016-12-08	criteria provided, single submitter	clinical testing	The N373T variant in the IDUA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N373T variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N373T variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In addition, this substitution occurs at a position that is not conserved across species. However, in silico analysis predicts this variant is probably damaging to the protein structure/function. We therefore interpret N373T as a variant of uncertain significance.
Invitae	RCV000970962	SCV001118573	likely benign	Mucopolysaccharidosis type 1	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002436237	SCV002751752	likely benign	Inborn genetic diseases	2021-12-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity	RCV003133251	SCV003809912	uncertain significance	not provided	2022-06-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003972556	SCV004789560	likely benign	IDUA-related condition	2024-02-20	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).