ClinVar Miner

Submissions for variant NM_001283009.2(RTEL1):c.208C>T (p.Arg70Cys)

gnomAD frequency: 0.00013  dbSNP: rs778775766
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000785019 SCV000923571 uncertain significance not specified 2019-01-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002535711 SCV003445439 uncertain significance Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 2022-06-20 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 70 of the RTEL1 protein (p.Arg70Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with RTEL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 634523). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 RCV003332247 SCV004039603 uncertain significance not provided 2023-03-29 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies suggest p.R70C does not appear to induce alternative lengthening of telomeres pathway by T-circles (Cardoso et al., 2017); Observed in the germline of an individual with Dyskeratosis Congenita whose telomere length was within normal limits, as well as a patient with a clinical diagnosis of Fanconi Anemia (Cardoso et al., 2017; Chang et al., 2023); This variant is associated with the following publications: (PMID: 27149842, 28495916, 36463940)

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