Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000255428 | SCV000321554 | likely pathogenic | not provided | 2019-08-05 | criteria provided, single submitter | clinical testing | 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: 31269755, 20301779, 16332973) |
Invitae | RCV001048156 | SCV001212146 | uncertain significance | Dyskeratosis congenita | 2020-01-19 | criteria provided, single submitter | clinical testing | 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. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individuals affected with dyskeratosis congenita (PMID: 16332973, Invitae). ClinVar contains an entry for this variant (Variation ID: 38941). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 408 of the DKC1 protein (p.Thr408Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. |
Genetic Services Laboratory, |
RCV000255428 | SCV002067418 | likely pathogenic | not provided | 2019-11-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000032192 | SCV000055782 | not provided | Dyskeratosis congenita, X-linked | no assertion provided | literature only |