Submissions for variant NM_000203.5(IDUA):c.1303C>T (p.Arg435Cys)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002786002	SCV003024988	uncertain significance	Mucopolysaccharidosis type 1	2024-01-25	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 435 of the IDUA protein (p.Arg435Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with IDUA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1986201). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on IDUA protein function. 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.
Ambry Genetics	RCV002786003	SCV003562903	uncertain significance	Inborn genetic diseases	2021-07-09	criteria provided, single submitter	clinical testing	The c.1303C>T (p.R435C) alteration is located in exon 9 (coding exon 9) of the IDUA gene. This alteration results from a C to T substitution at nucleotide position 1303, causing the arginine (R) at amino acid position 435 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV003134497	SCV003817605	uncertain significance	not provided	2020-06-09	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004750773	SCV005341856	uncertain significance	IDUA-related disorder	2024-04-03	no assertion criteria provided	clinical testing	The IDUA c.1303C>T variant is predicted to result in the amino acid substitution p.Arg435Cys. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.