Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002585011 | SCV003490268 | uncertain significance | Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 421 of the RTEL1 protein (p.Tyr421Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with RTEL1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Ambry Genetics | RCV002585010 | SCV003652361 | uncertain significance | Inborn genetic diseases | 2022-10-26 | criteria provided, single submitter | clinical testing | The c.1334A>G (p.Y445C) alteration is located in exon 15 (coding exon 14) of the RTEL1 gene. This alteration results from a A to G substitution at nucleotide position 1334, causing the tyrosine (Y) at amino acid position 445 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |