ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.1264G>A (p.Ala422Thr)

gnomAD frequency: 0.00001  dbSNP: rs1298013724
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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 RCV002561187 SCV001376723 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2023-04-28 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 936629). This variant has not been reported in the literature in individuals affected with TERT-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 422 of the TERT protein (p.Ala422Thr).
Ambry Genetics RCV004559927 SCV002679882 uncertain significance Dyskeratosis congenita 2022-02-26 criteria provided, single submitter clinical testing The p.A422T variant (also known as c.1264G>A), located in coding exon 2 of the TERT gene, results from a G to A substitution at nucleotide position 1264. The alanine at codon 422 is replaced by threonine, 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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