ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.2014C>T (p.Arg672Cys)

gnomAD frequency: 0.00024  dbSNP: rs368430301
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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 RCV002530122 SCV000650724 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2022-10-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 672 of the TERT protein (p.Arg672Cys). This variant is present in population databases (rs368430301, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of dyskeratosis congenita (PMID: 26136524, 30426156). ClinVar contains an entry for this variant (Variation ID: 471846). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
GeneDx RCV003325493 SCV004031815 uncertain significance not provided 2024-03-20 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with bone marrow failure and/or MDS or leukemia, at least one of whom had no features of dyskeratosis congenita on thorough examination (PMID: 26136524, 30426156, 31839986, 35106810); This variant is associated with the following publications: (PMID: 26136524, 30426156, 35106810, 31839986)
PreventionGenetics, part of Exact Sciences RCV004538044 SCV004720108 uncertain significance TERT-related disorder 2024-01-25 no assertion criteria provided clinical testing The TERT c.2014C>T variant is predicted to result in the amino acid substitution p.Arg672Cys. This variant has been reported in the heterozygous state in three individuals with features of dyskeratosis congenita (Ghemlas et al. 2015. PubMed ID: 26136524, suppl materials; Akram et al. 2018. PubMed ID: 30426156). This variant is reported in 0.048% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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