ClinVar Miner

Submissions for variant NM_016434.3(RTEL1):c.2812del (p.Leu938fs) (rs1449687529)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000700276 SCV000829024 pathogenic Dyskeratosis congenita, autosomal recessive, 5; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 3 2018-03-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu962Serfs*34) in the RTEL1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RTEL1-related disease. Loss-of-function variants in RTEL1 are known to be pathogenic (PMID: 23453664, 23959892, 25607374). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000826213 SCV000967779 likely pathogenic Dyskeratosis congenita 2018-08-13 criteria provided, single submitter clinical testing The p.Leu962SerfsX34 variant in RTEL1 has not been previously reported in indivi duals with short telomere syndromes or pulmonary fibrosis but has been identifie d in 1/23934 African chromosomes and 1/34396 Latino chromosomes by the Genome Ag gregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs771615945 ). This variant is predicted to cause a frameshift, which alters the protein?s a mino acid sequence beginning at position 496 and leads to a premature terminatio n codon 34 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Truncating variants in RTEL1 have been reported t o segregate with disease in several families with familial pulmonary fibrosis (S tuart 2015). In summary, although additional studies are required to fully estab lish its clinical significance, the p.Leu962SerfsX34 variant is likely pathogeni c. ACMG/AMP Criteria applied: PVS1, PM2.

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