Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001164845 | SCV001326996 | uncertain significance | Iodotyrosyl coupling defect | 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. |
Gene |
RCV001751295 | SCV002005113 | uncertain significance | not provided | 2019-07-22 | criteria provided, single submitter | clinical testing | Reported in the heterozygous state in two individuals with congenital hypothyroidism; one of these individuals harbored a nonsense variant in the TPO gene (Makretskaya et al., 2018); This variant is associated with the following publications: (PMID: 30240412) |
Institute for Clinical Genetics, |
RCV001751295 | SCV002010016 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002505745 | SCV002815881 | uncertain significance | Iodotyrosyl coupling defect; Autoimmune thyroid disease, susceptibility to, 3 | 2022-01-17 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001751295 | SCV003294831 | likely benign | not provided | 2024-01-28 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004526086 | SCV005039535 | uncertain significance | not specified | 2024-03-11 | criteria provided, single submitter | clinical testing | Variant summary: TG c.455G>A (p.Arg152His) results in a non-conservative amino acid change located in the Thyroglobulin type-1 domain (IPR000716) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00079 in 250730 control chromosomes in the gnomAD database, including 1 homozygote. c.455G>A has been reported in the literature as a VUS in heterozygous individuals affected with congenital hypothyroidism (e.g. Makretskaya_TG_PlosOne_2018). This report does not provide unequivocal conclusions about association of the variant with TG-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 30350900, 30240412). ClinVar contains an entry for this variant (Variation ID: 911984). Based on the evidence outlined above, the variant was classified as uncertain significance. |