Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003005075 | SCV003300002 | uncertain significance | Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 | 2022-03-17 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 944 of the RTEL1 protein (p.Lys944Glu). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid 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. |
Ambry Genetics | RCV003005076 | SCV003719036 | uncertain significance | Inborn genetic diseases | 2022-08-26 | criteria provided, single submitter | clinical testing | The c.2902A>G (p.K968E) alteration is located in exon 29 (coding exon 28) of the RTEL1 gene. This alteration results from a A to G substitution at nucleotide position 2902, causing the lysine (K) at amino acid position 968 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV004529187 | SCV004106583 | uncertain significance | RTEL1-related disorder | 2023-09-28 | criteria provided, single submitter | clinical testing | The RTEL1 c.2902A>G variant is predicted to result in the amino acid substitution p.Lys968Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0057% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/20-62324335-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |