Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics | RCV000516919 | SCV000614827 | uncertain significance | not specified | 2016-11-17 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV003480665 | SCV004223923 | pathogenic | not provided | 2023-03-14 | criteria provided, single submitter | clinical testing | PP3, PP4, PM2, PM5, PS3, PS4_supporting |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004586752 | SCV005076471 | likely pathogenic | Alzheimer disease 3 | 2024-04-25 | criteria provided, single submitter | clinical testing | Variant summary: PSEN1 c.799C>G (p.Pro267Ala) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250622 control chromosomes. c.799C>G has been reported in the literature in individuals affected with Alzheimer Disease, Type 3 (Ringman_2016). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Other variants that affect the same codon have been reported with functional and/or clinical evidence (p.P267S, p.P267L), suggesting the codon may be important for protein function. The following publication has been ascertained in the context of this evaluation (PMID: 26888304). ClinVar contains an entry for this variant (Variation ID: 448146). Based on the evidence outlined above, the variant was classified as likely pathogenic. |