ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.2422G>A (p.Val808Ile)

gnomAD frequency: 0.00003  dbSNP: rs200119385
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002530139 SCV000650745 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2023-11-11 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 808 of the TERT protein (p.Val808Ile). This variant is present in population databases (rs200119385, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TERT-related conditions. ClinVar contains an entry for this variant (Variation ID: 471864). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TERT protein function. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001508162 SCV001714129 uncertain significance not provided 2019-04-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV004559194 SCV002732877 uncertain significance Dyskeratosis congenita 2022-03-19 criteria provided, single submitter clinical testing The p.V808I variant (also known as c.2422G>A), located in coding exon 8 of the TERT gene, results from a G to A substitution at nucleotide position 2422. The valine at codon 808 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001508162 SCV005387220 uncertain significance not provided 2024-02-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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