ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.772C>T (p.His258Tyr)

dbSNP: rs1751206811
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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 RCV002561711 SCV001380836 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2019-08-21 criteria provided, single submitter clinical testing 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 missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tyrosine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TERT-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with tyrosine at codon 258 of the TERT protein (p.His258Tyr). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and tyrosine.
Ambry Genetics RCV004557415 SCV002669319 uncertain significance Dyskeratosis congenita 2022-07-19 criteria provided, single submitter clinical testing The p.H258Y variant (also known as c.772C>T), located in coding exon 2 of the TERT gene, results from a C to T substitution at nucleotide position 772. The histidine at codon 258 is replaced by tyrosine, 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.

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