ClinVar Miner

Submissions for variant NM_000484.4(APP):c.2125G>A (p.Gly709Ser)

gnomAD frequency: 0.00003  dbSNP: rs201269325
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000790930 SCV000930182 likely pathogenic Cerebral amyloid angiopathy, APP-related 2019-04-27 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000790931 SCV000930183 likely pathogenic Hereditary cerebral hemorrhage with amyloidosis 2019-04-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001869244 SCV002223862 uncertain significance Alzheimer disease 2023-11-06 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 709 of the APP protein (p.Gly709Ser). This variant is present in population databases (rs201269325, gnomAD 0.02%). This missense change has been observed in individual(s) with Parkinson disease and dementia (PMID: 25604855). ClinVar contains an entry for this variant (Variation ID: 638317). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt APP protein function with a positive predictive value of 95%. 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.

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