Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001350081 | SCV001544454 | uncertain significance | Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 | 2020-06-26 | 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. This variant disrupts the p.Gln223 amino acid residue in PSEN1. Other variant(s) that disrupt this residue have been observed in individuals with PSEN1-related conditions (PMID: 19912322, 22517194), which suggests that this may be a clinically significant amino acid residue. 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 individual(s) with PSEN1-related conditions (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with lysine at codon 223 of the PSEN1 protein (p.Gln223Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine. |