ClinVar Miner

Submissions for variant NM_001283009.2(RTEL1):c.971G>A (p.Arg324His)

gnomAD frequency: 0.00050  dbSNP: rs113684274
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000536702 SCV000653557 uncertain significance Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 2024-12-31 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 324 of the RTEL1 protein (p.Arg324His). This variant is present in population databases (rs113684274, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with RTEL1-related conditions. This variant is also known as c.1043G>A (p.Arg348His). ClinVar contains an entry for this variant (Variation ID: 473899). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The histidine 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.
Mendelics RCV000990339 SCV001141282 uncertain significance Dyskeratosis congenita, autosomal recessive 5 2019-05-28 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV001007595 SCV001167274 likely benign Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 2019-09-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV001829595 SCV002535816 uncertain significance Dyskeratosis congenita 2021-12-08 criteria provided, single submitter curation
Ambry Genetics RCV002404541 SCV002705845 uncertain significance Inborn genetic diseases 2024-02-27 criteria provided, single submitter clinical testing The c.1043G>A (p.R348H) alteration is located in exon 12 (coding exon 11) of the RTEL1 gene. This alteration results from a G to A substitution at nucleotide position 1043, causing the arginine (R) at amino acid position 348 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV000990339 SCV004209815 uncertain significance Dyskeratosis congenita, autosomal recessive 5 2022-12-06 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV003480684 SCV004225516 uncertain significance not provided 2022-10-03 criteria provided, single submitter clinical testing BP4
GeneDx RCV003480684 SCV005921451 uncertain significance not provided 2024-10-21 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001829595 SCV002095397 uncertain significance Dyskeratosis congenita 2019-11-11 no assertion criteria provided clinical testing

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