Submissions for variant NM_000203.4(IDUA):c.199A>T (p.Ser67Cys)

dbSNP: rs370442463

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000668547	SCV000793168	uncertain significance	Hurler syndrome	2017-07-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001156295	SCV001317783	uncertain significance	Mucopolysaccharidosis type 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001156295	SCV003472066	uncertain significance	Mucopolysaccharidosis type 1	2022-09-27	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 67 of the IDUA protein (p.Ser67Cys). This variant is present in population databases (rs370442463, gnomAD 0.03%). 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: 64576). 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.
Martin Pollak Laboratory, Beth Israel Deaconess Medical Center	RCV000054763	SCV000077453	unknown	not provided		no assertion criteria provided	not provided	Converted during submission to Uncertain significance.