ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.895G>T (p.Val299Leu)

dbSNP: rs756624928
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002532314 SCV000824132 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2018-02-28 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with TERT-related disease. This sequence change replaces valine with leucine at codon 299 of the TERT protein (p.Val299Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance 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.
Ambry Genetics RCV004559618 SCV002683989 uncertain significance Dyskeratosis congenita 2022-03-27 criteria provided, single submitter clinical testing The p.V299L variant (also known as c.895G>T), located in coding exon 2 of the TERT gene, results from a G to T substitution at nucleotide position 895. The valine at codon 299 is replaced by leucine, 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.

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