Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35138 | 105637;105638;105639 | chr2:178531203;178531202;178531201 | chr2:179395930;179395929;179395928 |
| N2AB | 33497 | 100714;100715;100716 | chr2:178531203;178531202;178531201 | chr2:179395930;179395929;179395928 |
| N2A | 32570 | 97933;97934;97935 | chr2:178531203;178531202;178531201 | chr2:179395930;179395929;179395928 |
| N2B | 26073 | 78442;78443;78444 | chr2:178531203;178531202;178531201 | chr2:179395930;179395929;179395928 |
| Novex-1 | 26198 | 78817;78818;78819 | chr2:178531203;178531202;178531201 | chr2:179395930;179395929;179395928 |
| Novex-2 | 26265 | 79018;79019;79020 | chr2:178531203;178531202;178531201 | chr2:179395930;179395929;179395928 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | rs771741670  |
-0.29 | 0.001 | N | 0.286 | 0.292 | None | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.68E-05 | 0 |
| M/T | rs771741670 |
-0.29 | 0.001 | N | 0.286 | 0.292 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| M/T | rs771741670 |
-0.29 | 0.001 | N | 0.286 | 0.292 | None | gnomAD-4.0.0 | 7.00186E-05 | None | None | None | None | N | None | 6.67343E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.56021E-05 | 0 | 1.12068E-04 |
| M/V | rs368992068 |
-0.387 | None | N | 0.053 | 0.137 | None | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 1.65399E-04 |
| M/V | rs368992068 |
-0.387 | None | N | 0.053 | 0.137 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 2.88351E-04 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/V | rs368992068 |
-0.387 | None | N | 0.053 | 0.137 | None | gnomAD-4.0.0 | 9.91398E-06 | None | None | None | None | N | None | 0 | 1.66661E-05 | None | 1.01338E-04 | 0 | None | 0 | 0 | 9.32295E-06 | 0 | 1.60087E-05 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4353 | ambiguous | 0.3751 | ambiguous | -1.321 | Destabilizing | None | N | 0.249 | neutral | None | None | None | None | N |
| M/C | 0.8152 | likely_pathogenic | 0.7272 | pathogenic | -1.03 | Destabilizing | 0.132 | N | 0.542 | neutral | None | None | None | None | N |
| M/D | 0.9204 | likely_pathogenic | 0.8724 | pathogenic | 0.25 | Stabilizing | 0.018 | N | 0.459 | neutral | None | None | None | None | N |
| M/E | 0.6351 | likely_pathogenic | 0.5372 | ambiguous | 0.326 | Stabilizing | 0.018 | N | 0.356 | neutral | None | None | None | None | N |
| M/F | 0.3246 | likely_benign | 0.3055 | benign | -0.276 | Destabilizing | 0.002 | N | 0.247 | neutral | None | None | None | None | N |
| M/G | 0.7817 | likely_pathogenic | 0.7167 | pathogenic | -1.679 | Destabilizing | 0.018 | N | 0.327 | neutral | None | None | None | None | N |
| M/H | 0.7018 | likely_pathogenic | 0.5787 | pathogenic | -0.9 | Destabilizing | 0.316 | N | 0.509 | neutral | None | None | None | None | N |
| M/I | 0.123 | likely_benign | 0.1114 | benign | -0.387 | Destabilizing | None | N | 0.052 | neutral | N | 0.346871076 | None | None | N |
| M/K | 0.3596 | ambiguous | 0.2466 | benign | -0.041 | Destabilizing | 0.013 | N | 0.339 | neutral | N | 0.45588684 | None | None | N |
| M/L | 0.1258 | likely_benign | 0.1168 | benign | -0.387 | Destabilizing | None | N | 0.047 | neutral | N | 0.367899709 | None | None | N |
| M/N | 0.6754 | likely_pathogenic | 0.5669 | pathogenic | -0.014 | Destabilizing | 0.116 | N | 0.559 | neutral | None | None | None | None | N |
| M/P | 0.9647 | likely_pathogenic | 0.9547 | pathogenic | -0.669 | Destabilizing | 0.051 | N | 0.501 | neutral | None | None | None | None | N |
| M/Q | 0.3959 | ambiguous | 0.302 | benign | 0.05 | Stabilizing | 0.116 | N | 0.354 | neutral | None | None | None | None | N |
| M/R | 0.3716 | ambiguous | 0.2533 | benign | 0.117 | Stabilizing | 0.013 | N | 0.491 | neutral | N | 0.425892007 | None | None | N |
| M/S | 0.5518 | ambiguous | 0.4691 | ambiguous | -0.716 | Destabilizing | 0.004 | N | 0.309 | neutral | None | None | None | None | N |
| M/T | 0.2996 | likely_benign | 0.2381 | benign | -0.507 | Destabilizing | 0.001 | N | 0.286 | neutral | N | 0.423409062 | None | None | N |
| M/V | 0.0721 | likely_benign | 0.0642 | benign | -0.669 | Destabilizing | None | N | 0.053 | neutral | N | 0.37393746 | None | None | N |
| M/W | 0.7773 | likely_pathogenic | 0.7014 | pathogenic | -0.292 | Destabilizing | 0.316 | N | 0.453 | neutral | None | None | None | None | N |
| M/Y | 0.7138 | likely_pathogenic | 0.6335 | pathogenic | -0.23 | Destabilizing | 0.018 | N | 0.449 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.