Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000422439 | SCV000227056 | other | not provided | 2018-05-25 | criteria provided, single submitter | clinical testing | |
Center for Pediatric Genomic Medicine, |
RCV000422439 | SCV000511059 | benign | not provided | 2017-01-27 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000674553 | SCV000799908 | likely benign | Hurler syndrome | 2018-05-16 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000708549 | SCV000837659 | other | Mucopolysaccharidosis type 1 | 2018-12-26 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000708549 | SCV001317785 | benign | Mucopolysaccharidosis type 1 | 2017-04-28 | 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194419 | SCV001363959 | benign | not specified | 2021-11-01 | criteria provided, single submitter | clinical testing | Variant summary: IDUA c.235G>A (p.Ala79Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0031 in 270526 control chromosomes, predominantly at a frequency of 0.031 within the African or African-American subpopulation in the gnomAD database, including 9 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 12 fold of the estimated maximal expected allele frequency for a pathogenic variant in IDUA causing Mucopolysaccharidosis Type 1 phenotype (0.0027), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. The variant, c.235G>A, also has been reported in the literature as a well-known pseudodeficiency allele, prevalent in the African American subpopulation. Individuals with pseudodeficiency allele(s) exhibit decreased alpha-L-iduronidase enzyme activity in biochemical assays using artificial substrates, but otherwise show no evidence of disease (see e.g. in Clarke_2016). Seven ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign pseudodeficiency allele (n=6) or VUS (n=1). Based on the evidence outlined above, the variant was classified as benign. |
Gene |
RCV000422439 | SCV001784074 | benign | not provided | 2018-09-18 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 27939258) |
Fulgent Genetics, |
RCV002500480 | SCV002811181 | likely benign | Calcium oxalate urolithiasis | 2021-07-19 | criteria provided, single submitter | clinical testing | |
Breakthrough Genomics, |
RCV000422439 | SCV005263615 | likely benign | not provided | criteria provided, single submitter | not provided | ||
Mayo Clinic Laboratories, |
RCV000422439 | SCV000801292 | uncertain significance | not provided | 2016-07-27 | no assertion criteria provided | clinical testing | |
Laboratory of Diagnostic Genome Analysis, |
RCV000422439 | SCV001800421 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV001194419 | SCV001921769 | benign | not specified | no assertion criteria provided | clinical testing | ||
Gene |
RCV000708549 | SCV002016347 | not provided | Mucopolysaccharidosis type 1 | no assertion provided | literature only | Pseudodeficiency variants |