Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003060899 | SCV003456038 | uncertain significance | Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 | 2024-08-17 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 737 of the RTEL1 protein (p.Asn737Ser). This variant is present in population databases (rs773705133, 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: 2147446). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The serine 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. |
| Neuberg Centre For Genomic Medicine, |
RCV003340614 | SCV004047086 | uncertain significance | Dyskeratosis congenita, autosomal recessive 5 | criteria provided, single submitter | clinical testing | The missense variant in c.2210A>G (p.Asn737Ser) in RTEL1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Asn737Ser variant is novel (not in any individuals) in 1000 Genomes and has allele frequency of 0.001602% in gnomAD database. This variant has not been reported to the ClinVar database. The amino acid Asn at position 737 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Asn737Ser in RTEL1 is predicted as conserved by PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain significance. | |
| Ambry Genetics | RCV004960964 | SCV005492600 | likely benign | Inborn genetic diseases | 2024-11-23 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |