Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001551970 | SCV001772579 | pathogenic | not provided | 2019-04-04 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that T66A leads to lowered levels of rRNA seudouridylation as well as an increase in cell apoptosis (Montanaro et al., 2002; Bellodi et al., 2013); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 10364516, 30577491, 21228398, 11851894, 23707062, 9888995, 22117216) |
Invitae | RCV003529927 | SCV004299723 | likely pathogenic | Dyskeratosis congenita | 2023-03-17 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 38946). This missense change has been observed in individual(s) with dyskeratosis congenita (PMID: 768476, 9888995). It has also been observed to segregate with disease in related individuals. This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 66 of the DKC1 protein (p.Thr66Ala). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects DKC1 function (PMID: 10591218, 16690864, 18212040, 23707062, 26571381, 30202881). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DKC1 protein function. |
Gene |
RCV000032197 | SCV000055788 | not provided | Dyskeratosis congenita, X-linked | no assertion provided | literature only | ||
Uni |
RCV000032197 | SCV000090829 | not provided | Dyskeratosis congenita, X-linked | no assertion provided | not provided |