ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.1151A>T (p.Gln384Leu)

dbSNP: rs1167344136
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002554308 SCV002172170 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2023-06-23 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. 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. ClinVar contains an entry for this variant (Variation ID: 1399208). 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 glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 384 of the TERT protein (p.Gln384Leu).
GeneDx RCV002284501 SCV002574448 uncertain significance not provided 2022-03-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004558716 SCV002622003 uncertain significance Dyskeratosis congenita 2022-03-03 criteria provided, single submitter clinical testing The p.Q384L variant (also known as c.1151A>T), located in coding exon 2 of the TERT gene, results from an A to T substitution at nucleotide position 1151. The glutamine at codon 384 is replaced by leucine, an amino acid with dissimilar 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.
Johns Hopkins Genomics, Johns Hopkins University RCV003320388 SCV004024536 uncertain significance Dyskeratosis congenita, autosomal dominant 2 2023-05-19 criteria provided, single submitter clinical testing This TERT missense variant is rare (<0.1%) in a large population dataset (gnomAD v3.1.2: 1/152072 total alleles; 0.0007%; no homozygotes). It has been reported in ClinVar (Variation ID 1399208), but has not been reported in the literature, to our knowledge. Two bioinformatic tools queried predict that this substitution would be tolerated. Glutamine at this position is conserved in very few species, with most species having a different amino acid, including one with leucine. We consider the clinical significance of c.1151A>T;p.Gln384Leu in TERT to be uncertain at this time.

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