Table 2 Interpretation of identified variants and their pathogenicity
Gene | Mutation | Function | Novel/known | SNP-ID | Mutation Tasting/SIFT/Provean/PolyPhen-2 | CADD score | Clinvar | GnomAD, ExAC, 1000 Genomes Frequency | ACMG | Publication (PMID) |
|---|---|---|---|---|---|---|---|---|---|---|
PSEN1 | NM_000021 p.Gln56Arg/c.167A > G | missense | Novel | rs754392688 | D/T/D/B | 16.57 | NA | 4/251420, 2/121286,0 | VUS: PM2 + PP3 + PP4 | NA |
PSEN1 | NM_000021 p.Ala136Val/c.407C > T | missense | Known | NA | D/D/D/P | 26.1 | NA | 0,0,0 | LP: PM1 + PM2 + PM5 + PP3 + PP4 | 33,973,882 |
PSEN1 | NM_000021 p.Met146Val/c.436A > G | missense | Known | rs63750306 | D/D/D/D | 24.4 | P | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 + PP5 | 9,712,537 |
PSEN1 | NM_000021 p.Leu174Pro /c.521 T > C | missense | Novel | NA | D/D/D/D | 25.3 | NA | 0,0,0 | LP: PM1 + PM2 + PM5 + PP3 + PP4 | NA |
PSEN1 | NM_000021 p.Leu226Arg/c.677 T > G | missense | Known | rs63749961 | D/D/D/D | 29.1 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 + PP5 | 15,196,662 |
PSEN1 | NM_000021 p.Ile249Leu/c.745A > C | missense | Known | rs1362575880 | D/D/N/D | 23.9 | LP | 1/251452,0,0 | P: PS1 + PM1 + PM2 + PP3 + PP4 | 31,914,229 |
PSEN1 | NM_000021 p.Leu262Ser/c.785 T > C | missense | Known | NA | D/D/D/D | 29.6 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 + PP5 | 30,954,774 |
PSEN1 | NM_000021 p.Glu273Gly/c.818A > G | missense | Known | NA | D/D/D/D | 29.8 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 + PP5 | 22,475,797 |
PSEN1 | NM_000021 p.Arg278Gly/c.832A > G | missense | Known | NA | D/D/D/D | 29.1 | NA | 0,0,0 | LP: PM1 + PM2 + PM5 + PP3 + PP4 | 37,712,079 |
PSEN1 | NM_000021 p.Ser289Pro/c.865 T > C | missense | Novel | NA | D/D/D/D | 32 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 | NA |
PSEN1 | NM_000021 p.Lys311Arg/ c.932A > G | missense | Known | rs115865530 | D/T/N/P | 14.04 | VUS | 35/251356, 16/118970,0 | VUS: PM2 + PP3 + PP4 + PP5 | 28,269,784 |
PSEN1 | NM_000021 p.Arg377Met/c.1130G > T | missense | Known | rs63751051 | D/D/D/D | 33 | NA | 0,0,0 | P: PS1 + PM1 + PM2 + PP3 + PP4 | 36,306,459 |
PSEN1 | NM_000021 p.Pro433Ser/c.1297C > T | missense | Known | rs1566657804 | D/D/D/D | 29.1 | LP | 0,0,0 | P: PS1 + PM1 + PM2 + PP3 + PP4 | 30,279,455 |
PSEN1 | NM_000021 p.Ile437Val/ c.1309A > G | missense | Known | rs764971634 | D/D/N/P | 22.2 | LP | 3/140276,1/121400,0 | LP: PM1 + PM2 + PP3 + PP4 + PP5 | 27,930,341 |
PSEN1 | NM_000021 p.Tyr466Cys/c.1397A > G | missense | Novel | NA | D/D/D/D | 26.8 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 | NA |
PSEN2 | NM_000447 p.Arg17Trp/c.49C > T | missense | Novel | rs199644116 | D/D/N/P | 24.8 | VUS | 1/140236, 4/121314,0 | LP: PM1 + PM2 + PP3 + PP4 | NA |
PSEN2 | NM_000447 p.Val214Leu/c.640G > T | missense | Known | rs574125890 | D/D/N/D | 24.3 | VUS | 15/140286,0,6/5008 | VUS: PM1 + PP3 + PP4 | 28,008,242 |
PSEN2 | NM_000447 p.Met239Thr/c.716 T > C | missense | Known | NA | D/D/D/D | 23.8 | NA | 0,0,0 | P: PS1 + PM1 + PM2 + PP3 + PP4 | 35,491,795 |
PSEN2 | NM_000447 p.Met298Thr/c.893 T > C | missense | Known | NA | D/D/N/D | 25.7 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 + PP5 | 30,954,774 |
PSEN2 | NM_000447 p.Phe331Tyr/c.992 T > A | missense | Novel | NA | D/T/N/D | 18.82 | NA | 0,0,0 | VUS: PM1 + PM2 + PP4 | NA |
APP | NM_000484 p.Asp197Asn/c.589G > A | missense | Novel | NA | D/D/N/D | 23.4 | NA | 0,0,0 | VUS: PM2 + PP3 + PP4 | NA |
APP | NM_000484 p.Ala235Val/c.704C > T | missense | Known | rs139819006 | D/T/D/B | 18.78 | VUS | 34/248594, 13/120884,0 | VUS: PM2 + PP3 + PP4 + PP5 | 26,242,991 |
APP | NM_000484 p.Asp252Val/c.755A > T | missense | Novel | NA | D/D/N/B | 22.2 | NA | 0,0,0 | VUS: PM2 + PP3 + PP4 | NA |
APP | NM_000484 p.Thr297Met/c.890C > T | missense | Known | rs557227002 | D/D/D/D | 28.7 | B | 51/251178, 25/121250,0 | VUS: PM2 + PP3 + PP4 + PP5 | 30,598,257 |