Table 3.
GRN and MAPT coding variants altering the amino acid sequence and respective PolyPhen and SIFT predictions of the impact of each variant
| Gene | Variant | Number of individuals | PolyPhen | SIFT | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Location in the gene | DNA change | Location in the protein | Predicted protein change | New variant? | PSIC score | Result | Score | Result | ||
| GRN | Ex 1 | c.55C>T | ParaGran | p.R19W | Already described | 5 | 0.447 | Benign | 0.03 | Affect protein function* |
| GRN | Ex 2 | c.163A>T | InterPara Gran | p.R55W | New | 1 | 1.622 | Possibly damaging | 0.14 | Tolerated |
| GRN | Ex 2 | c.205G>A | Gran G | p.A69T | New | 1 | 0.781 | Benign | 0.30 | Tolerated |
| GRN | Ex 4 | c.355_357del | InterGF | p.N119del | New | 1 | n.a. | n.a. | n.a. | n.a. |
| GRN | Ex 4 | c.359G>T | InterGF | p.S120Y | Already described | 2 | 1.627 | Possibly damaging | 0.09 | Tolerated |
| GRN | Ex 5 | c.545G>A | InterFB | p.T182M | Already described | 8 | 1.556 | Possibly damaging | 0.04 | Affect protein function |
| GRN | Ex 6 | c.662G>C | Gran B | p.C221S | New | 1 | 3.713 | Probably damaging | 0.01 | Affect protein function |
| GRN | Ex 7 | c.824G>A | InterBA | p.P275L | New | 1 | 3.146 | Probably damaging | 0.01 | Affect protein function |
| GRN | Ex 9 | c.1126C>T | Gran C | p.D376N | New | 2 | 0.32 | Benign | 1.00 | Tolerated |
| GRN | Ex 10 | c.1193G>A | Gran C | p.S398L | New | 1 | 0.895 | Benign | 0.14 | Tolerated |
| GRN | Ex 10 | c.1298G>A | InterCD | p.R433Q | Already described | 2 | 0.395 | Benign | 0.43 | Tolerated |
| GRN | Ex 11 | c.1544G>C | InterDE | p.G515A | Already described | 4 | 1.12 | Benign | 0.47 | Tolerated |
| GRN | Ex 12 | c.1691G>A | Gran E | p.R564H | New | 1 | 0.592 | Benign | 0.31 | Tolerated |
| MAPT | Ex 1 | c.50C>T | N-terminal | p.T17M | New | 1 | 1.557 | Possibly damaging | 0.02 | Affect protein function* |
| MAPT | Ex 1 | c.88A>G | N-terminal | p.T30A | New | 1 | 0.512 | Benign | 0.13 | Tolerated |
| MAPT | Ex 10 | c.898G>A | R2 | p.V300I | New | 1 | 0.114 | Benign | 0.07 | Tolerated |
*
This is a low confidence prediction (this substitution may have been predicted to affect function just because the sequences used were not evolutionarily diverse enough - for specific details please see http://sift.jcvi.org/).
Nucleotide numbering (“c.”) reflects cDNA numbering with +1 corresponding to the A of the ATG translation initiation codon in the reference sequences (GRN: NM_002087.2; MAPT: NM_005910.4), according to journal guidelines (www.hgvs.org/mutnomen). The initiation codon is codon 1. Protein numbering (“p.”) refers to sequences GRN: NP_002078.1 and MAPT: NP_058519.2.