Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000634480 | SCV000755796 | uncertain significance | Dyskeratosis congenita | 2018-11-01 | 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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TINF2-related disease. This variant is present in population databases (rs532096263, ExAC 0.02%). This sequence change replaces aspartic acid with valine at codon 446 of the TINF2 protein (p.Asp446Val). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and valine. |