ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.1615G>A (p.Glu539Lys)

gnomAD frequency: 0.00001  dbSNP: rs1203927893
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002544833 SCV000816546 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2022-09-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 539 of the TERT protein (p.Glu539Lys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 568528). 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 tolerated. 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.
GeneDx RCV001775960 SCV002012577 uncertain significance not provided 2024-06-09 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004559359 SCV002705798 uncertain significance Dyskeratosis congenita 2022-01-15 criteria provided, single submitter clinical testing The p.E539K variant (also known as c.1615G>A), located in coding exon 3 of the TERT gene, results from a G to A substitution at nucleotide position 1615. The glutamic acid at codon 539 is replaced by lysine, an amino acid with 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.
Baylor Genetics RCV003472196 SCV004203657 uncertain significance Dyskeratosis congenita, autosomal dominant 2 2023-06-06 criteria provided, single submitter clinical testing

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