Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000534839 | SCV000646125 | uncertain significance | Pitt-Hopkins syndrome | 2016-06-21 | criteria provided, single submitter | clinical testing | In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant is present in population databases (rs760934731, ExAC 0.002%) but has not been reported in the literature in individuals with a TCF4-related disease. This sequence change replaces threonine with asparagine at codon 81 of the TCF4 protein (p.Thr81Asn). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and asparagine. |