Submissions for variant NM_198253.3(TERT):c.952G>T (p.Asp318Tyr)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002710919	SCV003005937	uncertain significance	Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis	2023-06-20	criteria provided, single submitter	clinical testing	This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 318 of the TERT protein (p.Asp318Tyr). This variant has not been reported in the literature in individuals affected with TERT-related conditions. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TERT protein function. ClinVar contains an entry for this variant (Variation ID: 1963107).
GeneDx	RCV004784071	SCV005396060	uncertain significance	not provided	2024-05-06	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV004823056	SCV005512475	uncertain significance	Dyskeratosis congenita	2024-11-03	criteria provided, single submitter	clinical testing	The p.D318Y variant (also known as c.952G>T), located in coding exon 2 of the TERT gene, results from a G to T substitution at nucleotide position 952. The aspartic acid at codon 318 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.