Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000894593 | SCV001038588 | benign | not provided | 2024-10-07 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001131333 | SCV001290954 | uncertain significance | Deficiency of iodide peroxidase | 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. |
| Al Jalila Children’s Genomics Center, |
RCV001131333 | SCV001984140 | likely benign | Deficiency of iodide peroxidase | 2021-02-03 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155328 | SCV003844598 | likely benign | not specified | 2023-02-02 | criteria provided, single submitter | clinical testing | Variant summary: TPO c.2305C>T (p.Arg769Trp) results in a non-conservative amino acid change located in the Sushi/SCR/CCP domain (IPR000436) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0018 in 251490 control chromosomes, predominantly at a frequency of 0.02 within the African or African-American subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in TPO causing Deficiency Of Iodide Peroxidase phenotype (0.0071), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.2305C>T has been reported in the literature in individuals affected with Congenital Hypothyroidism without evidence for causality (Wang_2020, Wang_2021, Long_2018). At least one functional study reports this variant showed protein expression level is similar to WT but the specific enzymatic activity was reduced to 31% (Wang_2021). Three ClinVar submitters (evaluation after 2014) cite this variant as uncertain significance, likely benign and benign. Based on the evidence outlined above, the variant was classified as likely benign. |