ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.1657G>A (p.Val553Ile)

gnomAD frequency: 0.00001  dbSNP: rs749051614
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002537197 SCV000945134 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2021-09-08 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 553 of the TERT protein (p.Val553Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. 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 not been reported in the literature in individuals affected with TERT-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Sema4, Sema4 RCV002259020 SCV002533110 uncertain significance Dyskeratosis congenita 2021-10-19 criteria provided, single submitter curation
GeneDx RCV004773168 SCV005384118 uncertain significance not provided 2023-12-28 criteria provided, single submitter clinical testing 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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