Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000665392 | SCV000789508 | uncertain significance | Hurler syndrome | 2017-02-03 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001153898 | SCV001315208 | uncertain significance | Mucopolysaccharidosis type 1 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Labcorp Genetics |
RCV001153898 | SCV001417589 | uncertain significance | Mucopolysaccharidosis type 1 | 2022-09-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 263 of the IDUA protein (p.Arg263Trp). This variant is present in population databases (rs201268637, gnomAD 0.05%). This missense change has been observed in individual(s) with a positive newborn screening result for IDUA-related disease (PMID: 29143201, 30442156). ClinVar contains an entry for this variant (Variation ID: 550605). 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) performed at Invitae indicates that this missense variant is expected to disrupt IDUA protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282298 | SCV002570532 | uncertain significance | not specified | 2022-07-19 | criteria provided, single submitter | clinical testing | Variant summary: IDUA c.787A>T (p.Arg263Trp) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00013 in 193392 control chromosomes. This frequency is not higher than expected for a pathogenic variant in IDUA causing Mucopolysaccharidosis Type 1 (0.00013 vs 0.0027), allowing no conclusion about variant significance. c.787A>T has been reported in the literature in individuals with a positive newborn screening result for IDUA-related disease or diagnosed with pseudo mucopolysaccharidosis in homozygous or compound heterozygous state (examples: Burlina_2018, Donati_2018, Taylor_2019 and Polo_2020). These reports do not provide unequivocal conclusions about association of the variant with Mucopolysaccharidosis Type 1. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=5) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Revvity Omics, |
RCV000675604 | SCV003809998 | uncertain significance | not provided | 2023-10-30 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000675604 | SCV000801301 | uncertain significance | not provided | 2017-06-07 | no assertion criteria provided | clinical testing | |
Gene |
RCV001153898 | SCV002016349 | not provided | Mucopolysaccharidosis type 1 | no assertion provided | literature only | Pseudodeficiency variants | |
Natera, |
RCV001153898 | SCV002075313 | uncertain significance | Mucopolysaccharidosis type 1 | 2020-06-01 | no assertion criteria provided | clinical testing |