ClinVar Miner

Submissions for variant NM_001283009.2(RTEL1):c.3080C>T (p.Pro1027Leu)

gnomAD frequency: 0.00031  dbSNP: rs141782041
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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 RCV001247919 SCV001421372 uncertain significance Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 2022-11-04 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1027 of the RTEL1 protein (p.Pro1027Leu). This variant is present in population databases (rs141782041, gnomAD 0.1%). 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: 971998). 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 leucine 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.
Mayo Clinic Laboratories, Mayo Clinic RCV003481032 SCV004225526 uncertain significance not provided 2022-06-01 criteria provided, single submitter clinical testing BP4
Natera, Inc. RCV001835314 SCV002095531 uncertain significance Dyskeratosis congenita 2020-01-13 no assertion criteria provided clinical testing
Genetic Services Laboratory, University of Chicago RCV003151296 SCV003840013 uncertain significance not specified 2022-06-17 no assertion criteria provided clinical testing DNA sequence analysis of the RTEL1 gene demonstrated a sequence change, c.3152C>T (NM_032957.5), in exon 31 that results in an amino acid change, p.Pro1051Leu. This sequence change has been described in the gnomAD database with a frequency of 0.097% in the African/African American subpopulation (dbSNP rs141782041). The p.Pro1051Leu change affects a moderately conserved amino acid residue located in a domain of the RTEL1 protein that is not known to be functional. The p.Pro1051Leu substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in individuals with RTEL1-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Pro1051Leu change remains unknown at this time.

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