ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.1676C>G (p.Ser559Cys)

dbSNP: rs1579580077
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000788645 SCV000927832 uncertain significance not provided 2018-08-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV002397559 SCV002714615 uncertain significance Dyskeratosis congenita; Hereditary cancer-predisposing syndrome 2022-02-07 criteria provided, single submitter clinical testing The p.S559C variant (also known as c.1676C>G), located in coding exon 3 of the TERT gene, results from a C to G substitution at nucleotide position 1676. The serine at codon 559 is replaced by cysteine, an amino acid with 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.
Invitae RCV002535785 SCV003475638 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2022-04-29 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 559 of the TERT protein (p.Ser559Cys). This variant is not present in population databases (gnomAD no frequency). 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: 636733). 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 expected to disrupt 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.

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