ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.2775C>A (p.His925Gln)

dbSNP: rs34528119
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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 RCV002530511 SCV000770729 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2023-10-29 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 925 of the TERT protein (p.His925Gln). This variant is present in population databases (rs34528119, gnomAD 0.0009%). This missense change has been observed in individual(s) with chronic obstructive pulmonary disease (COPD) and/or pulmonary fibrosis (PMID: 20502709, 25562321). ClinVar contains an entry for this variant (Variation ID: 539210). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects TERT function (PMID: 20502709, 25562321). 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 RCV004568448 SCV005052972 uncertain significance Dyskeratosis congenita, autosomal dominant 2 2024-02-20 criteria provided, single submitter clinical testing
GeneDx RCV004702244 SCV005201964 uncertain significance not provided 2024-02-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20502709, 25562321)
Garcia Pulmonary Genetics Research Laboratory, Columbia University Irving Medical Center RCV002509491 SCV002547388 likely risk allele Pulmonary fibrosis 2022-06-09 no assertion criteria provided research

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