ClinVar Miner

Submissions for variant NM_001283009.2(RTEL1):c.3063C>A (p.His1021Gln)

gnomAD frequency: 0.00003  dbSNP: rs761907604
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000685815 SCV000813313 uncertain significance Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 2022-08-22 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1021 of the RTEL1 protein (p.His1021Gln). This variant is present in population databases (rs761907604, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with RTEL1-related conditions. This variant is also known as c.3135C>A (p.His1045Gln). ClinVar contains an entry for this variant (Variation ID: 566087). 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. 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.
Ambry Genetics RCV002544725 SCV003710016 uncertain significance Inborn genetic diseases 2020-12-10 criteria provided, single submitter clinical testing The c.3135C>A (p.H1045Q) alteration is located in exon 31 (coding exon 30) of the RTEL1 gene. This alteration results from a C to A substitution at nucleotide position 3135, causing the histidine (H) at amino acid position 1045 to be replaced by a glutamine (Q). The p.H1045Q alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic RCV003480761 SCV004225525 uncertain significance not provided 2022-03-08 criteria provided, single submitter clinical testing
Natera, Inc. RCV001835914 SCV002095530 uncertain significance Dyskeratosis congenita 2019-11-11 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004735743 SCV005367489 uncertain significance RTEL1-related disorder 2024-07-01 no assertion criteria provided clinical testing The RTEL1 c.3135C>A variant is predicted to result in the amino acid substitution p.His1045Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.044% of alleles in individuals of East Asian 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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