ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.1153C>T (p.Arg385Cys)

dbSNP: rs1751156834
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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 RCV002563029 SCV001394672 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2019-05-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 385 of the TERT protein (p.Arg385Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TERT-related conditions. 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 disruptive, but 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.
Genetic Services Laboratory, University of Chicago RCV001819920 SCV002066825 uncertain significance not specified 2021-01-21 criteria provided, single submitter clinical testing DNA sequence analysis of the TERT gene demonstrated a sequence change, c.1153C>T, in exon 2 that results in an amino acid change, p.Arg385Cys. This sequence change does not appear to have been previously described in patients with TERT-related disorders and has also not been described in the large population databases such as EXAC and gnomAD. The p.Arg385Cys change affects a highly conserved amino acid residue located in a domain of the TERT protein that is not known to be functional. The p.Arg385Cys substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Arg385Cys change remains unknown at this time.
Ambry Genetics RCV004557441 SCV005049187 uncertain significance Dyskeratosis congenita 2024-02-12 criteria provided, single submitter clinical testing The p.R385C variant (also known as c.1153C>T), located in coding exon 2 of the TERT gene, results from a C to T substitution at nucleotide position 1153. The arginine at codon 385 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 deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.

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