Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000299331 | SCV000389154 | benign | Familial hyperthyroidism due to mutations in TSH receptor | 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
| Illumina Laboratory Services, |
RCV000356472 | SCV000389155 | uncertain significance | Hypothyroidism due to TSH receptor mutations | 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. |
| Labcorp Genetics |
RCV000873340 | SCV001015319 | benign | not provided | 2024-01-29 | criteria provided, single submitter | clinical testing | |
| ITMI | RCV000122253 | SCV000086477 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
| Department of Pathology and Laboratory Medicine, |
RCV000873340 | SCV001548930 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The TSHR p.V721F variant was not identified in the literature but was identified in dbSNP (ID: rs61745409) and ClinVar (classified as uncertain significance by Illumina for congenital nongoitrous hypothyroidism 1; and as benign by Invitae Illumina for non-autoimmune hyperthyroidism). The variant was identified in control databases in 354 of 282230 chromosomes (2 homozygous) at a frequency of 0.001254, and was observed at the highest frequency in the Ashkenazi Jewish population in 291 of 10266 chromosomes (2 homozygous) (freq: 0.02835) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.V721 residue is not conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) do not suggest a high likelihood of impact the protein. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |