ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.2188G>A (p.Ala730Thr)

gnomAD frequency: 0.00004  dbSNP: rs761116773
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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 RCV002530131 SCV000650736 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 730 of the TERT protein (p.Ala730Thr). This variant is present in population databases (rs761116773, gnomAD 0.03%). This missense change has been observed in individual(s) with aplastic anemia (PMID: 30523342). ClinVar contains an entry for this variant (Variation ID: 471856). 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.
Baylor Genetics RCV003476300 SCV004203626 uncertain significance Dyskeratosis congenita, autosomal dominant 2 2023-08-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV004822104 SCV005512352 uncertain significance Dyskeratosis congenita 2024-08-29 criteria provided, single submitter clinical testing The p.A730T variant (also known as c.2188G>A), located in coding exon 6 of the TERT gene, results from a G to A substitution at nucleotide position 2188. The alanine at codon 730 is replaced by threonine, an amino acid with similar properties. This variant was reported in multiple individuals with features consistent with TERT-related disorder (Dressen A et al. Lancet Respir Med, 2018 Aug;6:603-614; Gutierrez-Rodrigues F et al. Genet Med, 2019 Jul;21:1594-1602). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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