ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.2813G>A (p.Arg938Gln)

dbSNP: rs199741493
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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 RCV002536010 SCV000964880 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2022-06-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 938 of the TERT protein (p.Arg938Gln). This variant is present in population databases (rs199741493, gnomAD 0.01%). 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: 665677). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV001293959 SCV001482671 uncertain significance Dyskeratosis congenita, autosomal dominant 2 2020-11-18 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV003222148 SCV003918352 uncertain significance not provided 2022-10-14 criteria provided, single submitter clinical testing 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
PreventionGenetics, part of Exact Sciences RCV004538131 SCV004106229 uncertain significance TERT-related disorder 2023-03-28 criteria provided, single submitter clinical testing The TERT c.2813G>A variant is predicted to result in the amino acid substitution p.Arg938Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.015% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-1264549-C-T). It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/665677/). 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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