ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.2267G>A (p.Arg756His)

gnomAD frequency: 0.00001  dbSNP: rs374206276
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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 RCV002535900 SCV000933461 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2022-10-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 756 of the TERT protein (p.Arg756His). This variant is present in population databases (rs374206276, gnomAD 0.006%). 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: 640939). 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 histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Ambry Genetics RCV004559658 SCV002733988 uncertain significance Dyskeratosis congenita 2022-02-12 criteria provided, single submitter clinical testing The p.R756H variant (also known as c.2267G>A), located in coding exon 6 of the TERT gene, results from a G to A substitution at nucleotide position 2267. The arginine at codon 756 is replaced by histidine, an amino acid with highly 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 RCV004569527 SCV005052988 uncertain significance Dyskeratosis congenita, autosomal dominant 2 2023-11-30 criteria provided, single submitter clinical testing

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