Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001307504 | SCV001496920 | uncertain significance | Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 | 2022-10-26 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1140 of the RTEL1 protein (p.Tyr1140Cys). This variant is not present in population databases (gnomAD no frequency). 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: 1009940). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV004034127 | SCV005029327 | uncertain significance | Inborn genetic diseases | 2024-01-27 | criteria provided, single submitter | clinical testing | The p.Y1164C variant (also known as c.3491A>G), located in coding exon 32 of the RTEL1 gene, results from an A to G substitution at nucleotide position 3491. The tyrosine at codon 1164 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001830240 | SCV002095563 | uncertain significance | Dyskeratosis congenita | 2021-09-08 | no assertion criteria provided | clinical testing | |
Prevention |
RCV004734109 | SCV005346260 | uncertain significance | RTEL1-related disorder | 2024-03-28 | no assertion criteria provided | clinical testing | The RTEL1 c.3491A>G variant is predicted to result in the amino acid substitution p.Tyr1164Cys. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |