Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002896115 | SCV003637734 | uncertain significance | Inborn genetic diseases | 2022-11-01 | criteria provided, single submitter | clinical testing | The c.124C>G (p.R42G) alteration is located in exon 4 (coding exon 2) of the PSEN1 gene. This alteration results from a C to G substitution at nucleotide position 124, causing the arginine (R) at amino acid position 42 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003777888 | SCV004591434 | uncertain significance | Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 | 2023-07-26 | criteria provided, single submitter | clinical testing | 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 not expected to disrupt PSEN1 protein function. This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 42 of the PSEN1 protein (p.Arg42Gly). This variant is present in population databases (rs140189461, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with PSEN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2305774). 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. |