ClinVar Miner

Submissions for variant NM_000203.5(IDUA):c.1001T>G (p.Leu334Arg)

gnomAD frequency: 0.00006  dbSNP: rs753372554
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001536744 SCV001753550 uncertain significance not provided 2019-11-12 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001832731 SCV003449962 uncertain significance Mucopolysaccharidosis type 1 2022-09-27 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 334 of the IDUA protein (p.Leu334Arg). This variant is present in population databases (rs753372554, gnomAD 0.008%). 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: 1179703). 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.
Revvity Omics, Revvity RCV001536744 SCV003809942 uncertain significance not provided 2021-04-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV004631722 SCV005121530 uncertain significance Inborn genetic diseases 2024-06-16 criteria provided, single submitter clinical testing The c.1001T>G (p.L334R) alteration is located in exon 8 (coding exon 8) of the IDUA gene. This alteration results from a T to G substitution at nucleotide position 1001, causing the leucine (L) at amino acid position 334 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001832731 SCV002075327 uncertain significance Mucopolysaccharidosis type 1 2020-06-19 no assertion criteria provided clinical testing

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