Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000339398 | SCV000329339 | pathogenic | not provided | 2022-12-27 | criteria provided, single submitter | clinical testing | Observed as a single heterozygous variant in multiple individuals in published literature with congenital hypothyroidism (Tan et al., 2016; Sasivari et al., 2019); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 24423310, 34539567, 34200080, 27557340, 28633507, 31541602, 28648510, 17121535, 29650690, 31980526, 31589614, 33651715) |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000604013 | SCV000745411 | pathogenic | Thyroid dyshormonogenesis 6 | 2015-09-21 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000604013 | SCV000915685 | likely pathogenic | Thyroid dyshormonogenesis 6 | 2018-10-30 | criteria provided, single submitter | clinical testing | The DUOX2 c.602dupG (p.Gln202ThrfsTer99) variant results in a frameshift and is predicted to result in premature termination of the protein. The p.Gln202ThrfsTer99 variant has been reported in two studies and is found in a total of four individuals with congenital hypothyroidism, including in three in a compound heterozygous state (two of the individuals were siblings) and in one in a heterozygous state in whom a second variant was not identified (Pfarr et al. 2006; Muzza et al. 2013). The variant is also found in two unaffected heterozygous individuals. The p.Gln202ThrfsTer99 variant was absent from 110 controls, but is reported at a frequency of 0.001508 in the European (non-Finnish) population of the Genome Aggregation Database. cDNA from an affected individual showed only the wildtype allele, suggesting the skipping or the degradation of the mutated allele. Skipping of exon 5 has been demonstrated in the cDNA from lymphocytes, thyroid, testis, pituitary, and orbital fat of control subjects indicating the existence of a physiologically occurring alternative splice variant (Muzza et al. 2013). Based on the collective evidence, the p.Gln202ThrfsTer99 variant is classified as likely pathogenic for congenital hypothyroidism. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV000339398 | SCV000961931 | pathogenic | not provided | 2023-10-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln202Thrfs*99) in the DUOX2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DUOX2 are known to be pathogenic (PMID: 12110737, 18765513, 21565790, 24423310, 24735383). This variant is present in population databases (rs567500345, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with congenital primary hypothyroidism (PMID: 17121535, 24423310, 27557340). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as ins602g. ClinVar contains an entry for this variant (Variation ID: 279800). For these reasons, this variant has been classified as Pathogenic. |
Rady Children's Institute for Genomic Medicine, |
RCV000604013 | SCV001443717 | pathogenic | Thyroid dyshormonogenesis 6 | 2019-11-21 | criteria provided, single submitter | clinical testing | This variant is sometimes referred to as ins602gfsX300 and ins602g in the literature.This frameshifting variant in exon 6 of 34 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function. It is present in the heterozygous state in the gnomAD population database at a frequency of 0.08599% (153/177920). This variant has been reported in the literature as compound heterozygous or as heterozygous without a second variant identified in individuals with congenital primary hypothyroidism (PMID: 17121535, 24423310). Skipping of exon 5 due to this alteration has been reported (PMID: 17121535); however, an additional study showed that skipping of exon 5 occurs naturally in the RNA from lymphocytes, thyroid, testis, pituitary, and orbital fat of control subjects (PMID: 24423310). ClinVar contains an entry for this variant (Variation ID: 279800). Based on the available evidence the c.602dup (p.Gln202ThrfsTer99) variant is classified as Pathogenic. |
Knight Diagnostic Laboratories, |
RCV000604013 | SCV001448969 | pathogenic | Thyroid dyshormonogenesis 6 | 2017-11-10 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000604013 | SCV002021809 | pathogenic | Thyroid dyshormonogenesis 6 | 2020-01-17 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000339398 | SCV002064523 | pathogenic | not provided | 2020-07-27 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000604013 | SCV002778417 | pathogenic | Thyroid dyshormonogenesis 6 | 2022-01-21 | criteria provided, single submitter | clinical testing | |
Diagnostic Laboratory, |
RCV000604013 | SCV000733452 | pathogenic | Thyroid dyshormonogenesis 6 | no assertion criteria provided | clinical testing | ||
Polak associated Lab, |
RCV001270329 | SCV001450552 | likely pathogenic | Congenital hypothyroidism | no assertion criteria provided | clinical testing | ||
Clinical Genetics Laboratory, |
RCV000604013 | SCV001745318 | pathogenic | Thyroid dyshormonogenesis 6 | 2021-01-15 | no assertion criteria provided | clinical testing | |
Clinical Genetics, |
RCV000339398 | SCV001923587 | pathogenic | not provided | no assertion criteria provided | clinical testing |