ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.508G>A (p.Val170Met)

gnomAD frequency: 0.00001  dbSNP: rs387907248
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002513271 SCV000770704 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 170 of the TERT protein (p.Val170Met). This variant is present in population databases (rs387907248, gnomAD 0.001%). This missense change has been observed in individual(s) with aplastic anemia and pulmonary fibrosis (PMID: 21436073, 24833766, 35776903). ClinVar contains an entry for this variant (Variation ID: 36947). 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 95%. Experimental studies have shown that this missense change affects TERT function (PMID: 21436073). 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.
Fulgent Genetics, Fulgent Genetics RCV000765805 SCV000897195 uncertain significance Interstitial lung disease 2; Aplastic anemia; Dyskeratosis congenita, autosomal dominant 1; Acute myeloid leukemia; Dyskeratosis congenita, autosomal dominant 2; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1; Melanoma, cutaneous malignant, susceptibility to, 9 2022-04-07 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003407372 SCV004102899 uncertain significance TERT-related condition 2023-07-13 criteria provided, single submitter clinical testing The TERT c.508G>A variant is predicted to result in the amino acid substitution p.Val170Met. This variant has been reported in several individuals with aplastic anaemia and pulmonary fibrosis (Parry et al. 2011. PubMed ID: 21436073; Silhan et al. 2014. PubMed ID: 24833766; Gutierrez-Rodrigues et al. 2018. PubMed ID: 30523342). Telomerase activity assay showed that this variant may decrease enzyme activity (Parry et al. 2011. PubMed ID: 21436073). This variant is reported in 0.0012% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-1294493-C-T). Although we suspect this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV003473153 SCV004203652 uncertain significance Dyskeratosis congenita, autosomal dominant 2 2023-06-22 criteria provided, single submitter clinical testing
OMIM RCV000030628 SCV000053306 pathogenic Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 2011-05-26 no assertion criteria provided literature only

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