ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.2935C>T (p.Arg979Trp) (rs199422305)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000648885 SCV000770706 uncertain significance Idiopathic fibrosing alveolitis, chronic form; Dyskeratosis congenita, autosomal dominant, 2 2019-06-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 979 of the TERT protein (p.Arg979Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual affected with dyskeratosis congenita and pulmonary fibrosis, as well as in an individual with agranulocytosis and aplastic anemia (PMID: 15885610, 26360549). In the former individual, two other first degree relatives were similarly affected, but mutation analysis was not conducted, therefore it could not be determined whether this variant segregated with disease. ClinVar contains an entry for this variant (Variation ID: 39118). Experimental studies have shown that this missense change interferes with TERT enzymatic activity and processivity. In addition, analysis of patient-derived cells with the p.Arg979Trp variant displayed shortened telomere lengths. (PMID: 28154186, 23901009, 21602826, 12167716). 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.
GeneReviews RCV000032390 SCV000056046 pathologic Dyskeratosis congenita, autosomal dominant 1 2012-05-10 no assertion criteria provided curation Converted during submission to Pathogenic.
Radiation Cancer Biology Lab, University of Rajasthan Jaipur RCV000144245 SCV000189364 not provided Aplastic anemia no assertion provided not provided

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