Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23273 | 70042;70043;70044 | chr2:178576315;178576314;178576313 | chr2:179441042;179441041;179441040 |
| N2AB | 21632 | 65119;65120;65121 | chr2:178576315;178576314;178576313 | chr2:179441042;179441041;179441040 |
| N2A | 20705 | 62338;62339;62340 | chr2:178576315;178576314;178576313 | chr2:179441042;179441041;179441040 |
| N2B | 14208 | 42847;42848;42849 | chr2:178576315;178576314;178576313 | chr2:179441042;179441041;179441040 |
| Novex-1 | 14333 | 43222;43223;43224 | chr2:178576315;178576314;178576313 | chr2:179441042;179441041;179441040 |
| Novex-2 | 14400 | 43423;43424;43425 | chr2:178576315;178576314;178576313 | chr2:179441042;179441041;179441040 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs1233267673  |
None | 0.183 | N | 0.374 | 0.208 | 0.275215494804 | gnomAD-4.0.0 | 1.70038E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.99441E-06 | 0 | 0 |
| T/I | None | None | 0.001 | N | 0.154 | 0.166 | 0.31077124679 | gnomAD-4.0.0 | 7.03575E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.12475E-07 | 0 | 0 |
| T/S | rs371067787 |
-1.117 | 0.183 | N | 0.384 | 0.127 | 0.231231049324 | gnomAD-2.1.1 | 4.81E-06 | None | None | None | None | I | None | 6.83E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/S | rs371067787 |
-1.117 | 0.183 | N | 0.384 | 0.127 | 0.231231049324 | gnomAD-4.0.0 | 7.03575E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.12475E-07 | 0 | 0 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0988 | likely_benign | 0.096 | benign | -0.703 | Destabilizing | 0.183 | N | 0.374 | neutral | N | 0.489641305 | None | None | I |
| T/C | 0.3877 | ambiguous | 0.3643 | ambiguous | -0.399 | Destabilizing | 0.983 | D | 0.384 | neutral | None | None | None | None | I |
| T/D | 0.4941 | ambiguous | 0.4714 | ambiguous | -0.095 | Destabilizing | 0.264 | N | 0.407 | neutral | None | None | None | None | I |
| T/E | 0.3041 | likely_benign | 0.2871 | benign | -0.126 | Destabilizing | 0.004 | N | 0.153 | neutral | None | None | None | None | I |
| T/F | 0.2778 | likely_benign | 0.252 | benign | -0.863 | Destabilizing | 0.716 | D | 0.484 | neutral | None | None | None | None | I |
| T/G | 0.3056 | likely_benign | 0.2874 | benign | -0.925 | Destabilizing | 0.593 | D | 0.459 | neutral | None | None | None | None | I |
| T/H | 0.2488 | likely_benign | 0.2238 | benign | -1.248 | Destabilizing | 0.983 | D | 0.441 | neutral | None | None | None | None | I |
| T/I | 0.1191 | likely_benign | 0.1113 | benign | -0.214 | Destabilizing | 0.001 | N | 0.154 | neutral | N | 0.491932493 | None | None | I |
| T/K | 0.1268 | likely_benign | 0.1121 | benign | -0.672 | Destabilizing | 0.418 | N | 0.398 | neutral | None | None | None | None | I |
| T/L | 0.085 | likely_benign | 0.0799 | benign | -0.214 | Destabilizing | 0.001 | N | 0.154 | neutral | None | None | None | None | I |
| T/M | 0.087 | likely_benign | 0.0871 | benign | 0.105 | Stabilizing | 0.716 | D | 0.412 | neutral | None | None | None | None | I |
| T/N | 0.1605 | likely_benign | 0.1531 | benign | -0.48 | Destabilizing | 0.523 | D | 0.429 | neutral | N | 0.48603368 | None | None | I |
| T/P | 0.4684 | ambiguous | 0.4415 | ambiguous | -0.345 | Destabilizing | 0.921 | D | 0.44 | neutral | N | 0.511988748 | None | None | I |
| T/Q | 0.1998 | likely_benign | 0.1917 | benign | -0.711 | Destabilizing | 0.716 | D | 0.439 | neutral | None | None | None | None | I |
| T/R | 0.1211 | likely_benign | 0.1078 | benign | -0.413 | Destabilizing | 0.716 | D | 0.437 | neutral | None | None | None | None | I |
| T/S | 0.1303 | likely_benign | 0.1296 | benign | -0.758 | Destabilizing | 0.183 | N | 0.384 | neutral | N | 0.500589261 | None | None | I |
| T/V | 0.1142 | likely_benign | 0.1086 | benign | -0.345 | Destabilizing | 0.049 | N | 0.308 | neutral | None | None | None | None | I |
| T/W | 0.6006 | likely_pathogenic | 0.5536 | ambiguous | -0.781 | Destabilizing | 0.983 | D | 0.484 | neutral | None | None | None | None | I |
| T/Y | 0.3466 | ambiguous | 0.3207 | benign | -0.558 | Destabilizing | 0.836 | D | 0.477 | neutral | None | None | None | None | I |
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.