ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.708G>C (p.Lys236Asn)

gnomAD frequency: 0.00001  dbSNP: rs1250720718
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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 RCV002573436 SCV002262286 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2021-08-07 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with TERT-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with asparagine at codon 236 of the TERT protein (p.Lys236Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. 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. 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.
Ambry Genetics RCV004558777 SCV003869047 uncertain significance Dyskeratosis congenita 2023-03-03 criteria provided, single submitter clinical testing The p.K236N variant (also known as c.708G>C), located in coding exon 2 of the TERT gene, results from a G to C substitution at nucleotide position 708. The lysine at codon 236 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003442984 SCV004169771 uncertain significance not provided 2023-05-09 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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