ClinVar Miner

Submissions for variant NM_001283009.2(RTEL1):c.763G>A (p.Val255Met)

gnomAD frequency: 0.00004  dbSNP: rs778675789
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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 RCV001042911 SCV001206620 uncertain significance Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 2024-12-23 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 255 of the RTEL1 protein (p.Val255Met). This variant is present in population databases (rs778675789, gnomAD 0.01%). 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: 840820). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Johns Hopkins Genomics, Johns Hopkins University RCV001805989 SCV002051778 uncertain significance Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 2021-11-16 criteria provided, single submitter clinical testing This RTEL1 variant (rs778675789) is rare (<0.1%) in a large population dataset (gnomAD: 9/232248 total alleles; 0.003875%; no homozygotes). It has not been reported in the literature to our knowledge, but there is an entry in ClinVar. Of three bioinformatics tools queried, two predict that the substitution would be damaging, while one predicts that it would be tolerated. The valine residue at this position is evolutionarily conserved across most species assessed. We consider the clinical significance of c.763G>A to be uncertain at this time.
Sema4, Sema4 RCV001827258 SCV002535807 uncertain significance Dyskeratosis congenita 2022-01-06 criteria provided, single submitter curation
Ambry Genetics RCV004958389 SCV005492487 uncertain significance Inborn genetic diseases 2024-10-04 criteria provided, single submitter clinical testing The p.V255M variant (also known as c.763G>A), located in coding exon 8 of the RTEL1 gene, results from a G to A substitution at nucleotide position 763. The valine at codon 255 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Natera, Inc. RCV001827258 SCV002095382 uncertain significance Dyskeratosis congenita 2020-12-18 no assertion criteria provided clinical testing

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