Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000809717 | SCV000949887 | uncertain significance | Alzheimer disease | 2021-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 344 of the APP protein (p.Ala344Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 653874). This variant has not been reported in the literature in individuals affected with APP-related conditions. This variant is present in population databases (rs201045185, ExAC 0.006%). |