ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.568G>A (p.Ala190Thr)

gnomAD frequency: 0.00001  dbSNP: rs377016753
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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 RCV002562609 SCV001398644 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2022-06-03 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 953957). 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 not expected to disrupt TERT protein function. This variant has not been reported in the literature in individuals affected with TERT-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 190 of the TERT protein (p.Ala190Thr).
Ambry Genetics RCV004557457 SCV003858469 uncertain significance Dyskeratosis congenita 2022-11-30 criteria provided, single submitter clinical testing The p.A190T variant (also known as c.568G>A), located in coding exon 2 of the TERT gene, results from a G to A substitution at nucleotide position 568. The alanine at codon 190 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.
Genetic Services Laboratory, University of Chicago RCV003151291 SCV003840119 uncertain significance not specified 2022-09-09 no assertion criteria provided clinical testing DNA sequence analysis of the TERT gene demonstrated a sequence change, c.568G>A, in exon 2 that results in an amino acid change, p.Ala190Thr. This sequence change does not appear to have been previously described in individuals with TERT-related disorders and has also not been described in population databases such as ExAC and gnomAD (dbSNP rs377016753). The p.Ala190Thr change affects a poorly conserved amino acid residue located in a domain of the TERT protein that is not known to be functional. The p.Ala190Thr substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Ala190Thr change remains unknown at this time.

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