Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002561724 | SCV001381430 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis | 2022-03-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 327 of the TERT protein (p.Glu327Gln). 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 variant has not been reported in the literature in individuals affected with TERT-related conditions. ClinVar contains an entry for this variant (Variation ID: 940394). 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 expected to disrupt TERT 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 | RCV004557418 | SCV002693995 | uncertain significance | Dyskeratosis congenita | 2022-02-23 | criteria provided, single submitter | clinical testing | The p.E327Q variant (also known as c.979G>C), located in coding exon 2 of the TERT gene, results from a G to C substitution at nucleotide position 979. The glutamic acid at codon 327 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Baylor Genetics | RCV003473755 | SCV004203636 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2 | 2023-08-04 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004538452 | SCV004716142 | uncertain significance | TERT-related disorder | 2023-12-14 | no assertion criteria provided | clinical testing | The TERT c.979G>C variant is predicted to result in the amino acid substitution p.Glu327Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |