ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.887A>C (p.His296Pro) (rs778187343)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000378796 SCV000452700 uncertain significance Dyskeratosis congenita, autosomal dominant, 2 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.
Illumina Clinical Services Laboratory,Illumina RCV000283392 SCV000452701 uncertain significance Aplastic anemia 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.
Illumina Clinical Services Laboratory,Illumina RCV000322037 SCV000452702 benign Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1 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.
Invitae RCV000471556 SCV000551510 uncertain significance Idiopathic fibrosing alveolitis, chronic form; Dyskeratosis congenita, autosomal dominant, 2 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces histidine with proline at codon 296 of the TERT protein (p.His296Pro). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and proline. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in an individual affected with primary liver cancer (PMID: 28677271). ClinVar contains an entry for this variant (Variation ID: 268080). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In addition, an experimental study has shown that recombinant proteins containing this variant were expressed at similar levels as the wild-type TERT protein in cultured human cell lines (PMID: 28677271). However, the clinical significance of these results is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000765804 SCV000897194 uncertain significance Idiopathic fibrosing alveolitis, chronic form; Aplastic anemia; Dyskeratosis congenita, autosomal dominant 1; Acute myeloid leukemia; Dyskeratosis congenita, autosomal dominant, 2; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1; Cutaneous malignant melanoma 9 2018-10-31 criteria provided, single submitter clinical testing
Metabolic Liver Diseases Lab,Fondazione IRCCS Ca Granda Policlinico, University of Milan RCV000503276 SCV000328547 uncertain significance Hepatocellular carcinoma 2016-06-01 no assertion criteria provided case-control

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