ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.718C>T (p.Arg240Cys)

dbSNP: rs1252662816
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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 RCV002555371 SCV002171484 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2020-11-10 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 240 of the TERT protein (p.Arg240Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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) performed at Invitae indicates that this missense variant is not expected to disrupt TERT protein function. This variant has not been reported in the literature in individuals with TERT-related conditions.
Ambry Genetics RCV004558725 SCV005048978 uncertain significance Dyskeratosis congenita 2023-10-22 criteria provided, single submitter clinical testing The p.R240C variant (also known as c.718C>T), located in coding exon 2 of the TERT gene, results from a C to T substitution at nucleotide position 718. The arginine at codon 240 is replaced by cysteine, an amino acid with highly dissimilar 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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