Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23288 | 70087;70088;70089 | chr2:178576270;178576269;178576268 | chr2:179440997;179440996;179440995 |
| N2AB | 21647 | 65164;65165;65166 | chr2:178576270;178576269;178576268 | chr2:179440997;179440996;179440995 |
| N2A | 20720 | 62383;62384;62385 | chr2:178576270;178576269;178576268 | chr2:179440997;179440996;179440995 |
| N2B | 14223 | 42892;42893;42894 | chr2:178576270;178576269;178576268 | chr2:179440997;179440996;179440995 |
| Novex-1 | 14348 | 43267;43268;43269 | chr2:178576270;178576269;178576268 | chr2:179440997;179440996;179440995 |
| Novex-2 | 14415 | 43468;43469;43470 | chr2:178576270;178576269;178576268 | chr2:179440997;179440996;179440995 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/K | None | None | 0.024 | N | 0.301 | 0.119 | 0.486851695374 | gnomAD-4.0.0 | 6.86314E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0087E-06 | 0 | 0 |
| I/M | rs368867993  |
-0.423 | 0.002 | N | 0.163 | 0.048 | None | gnomAD-2.1.1 | 1.45944E-04 | None | None | None | None | N | None | 9.17661E-04 | 3.76157E-04 | None | 0 | 0 | None | 0 | None | 0 | 3.2E-05 | 1.43472E-04 |
| I/M | rs368867993 |
-0.423 | 0.002 | N | 0.163 | 0.048 | None | gnomAD-3.1.2 | 2.49829E-04 | None | None | None | None | N | None | 7.23903E-04 | 1.96541E-04 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 9.56938E-04 |
| I/M | rs368867993 |
-0.423 | 0.002 | N | 0.163 | 0.048 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/M | rs368867993 |
-0.423 | 0.002 | N | 0.163 | 0.048 | None | gnomAD-4.0.0 | 1.00045E-04 | None | None | None | None | N | None | 6.5594E-04 | 4.21258E-04 | None | 0 | 0 | None | 0 | 8.29738E-04 | 5.8571E-05 | 0 | 2.08728E-04 |
| I/R | None | None | 0.055 | N | 0.373 | 0.143 | 0.499281839539 | gnomAD-4.0.0 | 6.86314E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0087E-07 | 0 | 0 |
| I/T | rs373121875 |
-1.03 | None | N | 0.213 | 0.084 | None | gnomAD-2.1.1 | 4.12E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.11E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2281 | likely_benign | 0.2695 | benign | -1.519 | Destabilizing | 0.007 | N | 0.223 | neutral | None | None | None | None | N |
| I/C | 0.4428 | ambiguous | 0.4458 | ambiguous | -0.699 | Destabilizing | 0.356 | N | 0.306 | neutral | None | None | None | None | N |
| I/D | 0.4265 | ambiguous | 0.4734 | ambiguous | -1.15 | Destabilizing | 0.016 | N | 0.316 | neutral | None | None | None | None | N |
| I/E | 0.1935 | likely_benign | 0.2221 | benign | -1.158 | Destabilizing | None | N | 0.257 | neutral | None | None | None | None | N |
| I/F | 0.1334 | likely_benign | 0.1332 | benign | -1.087 | Destabilizing | 0.072 | N | 0.259 | neutral | None | None | None | None | N |
| I/G | 0.4099 | ambiguous | 0.4525 | ambiguous | -1.819 | Destabilizing | 0.072 | N | 0.308 | neutral | None | None | None | None | N |
| I/H | 0.2184 | likely_benign | 0.2262 | benign | -0.993 | Destabilizing | 0.628 | D | 0.344 | neutral | None | None | None | None | N |
| I/K | 0.1113 | likely_benign | 0.1232 | benign | -1.052 | Destabilizing | 0.024 | N | 0.301 | neutral | N | 0.462297445 | None | None | N |
| I/L | 0.0941 | likely_benign | 0.0957 | benign | -0.772 | Destabilizing | 0.001 | N | 0.143 | neutral | N | 0.450043011 | None | None | N |
| I/M | 0.0836 | likely_benign | 0.0855 | benign | -0.517 | Destabilizing | 0.002 | N | 0.163 | neutral | N | 0.475133456 | None | None | N |
| I/N | 0.1162 | likely_benign | 0.1318 | benign | -0.839 | Destabilizing | 0.072 | N | 0.376 | neutral | None | None | None | None | N |
| I/P | 0.8839 | likely_pathogenic | 0.9053 | pathogenic | -0.99 | Destabilizing | 0.136 | N | 0.376 | neutral | None | None | None | None | N |
| I/Q | 0.1336 | likely_benign | 0.1467 | benign | -1.036 | Destabilizing | 0.072 | N | 0.371 | neutral | None | None | None | None | N |
| I/R | 0.1111 | likely_benign | 0.12 | benign | -0.393 | Destabilizing | 0.055 | N | 0.373 | neutral | N | 0.455160829 | None | None | N |
| I/S | 0.1603 | likely_benign | 0.1908 | benign | -1.364 | Destabilizing | 0.016 | N | 0.274 | neutral | None | None | None | None | N |
| I/T | 0.1243 | likely_benign | 0.1561 | benign | -1.263 | Destabilizing | None | N | 0.213 | neutral | N | 0.414218284 | None | None | N |
| I/V | 0.0706 | likely_benign | 0.0699 | benign | -0.99 | Destabilizing | None | N | 0.085 | neutral | N | 0.405078725 | None | None | N |
| I/W | 0.6436 | likely_pathogenic | 0.6428 | pathogenic | -1.178 | Destabilizing | 0.864 | D | 0.343 | neutral | None | None | None | None | N |
| I/Y | 0.3379 | likely_benign | 0.3399 | benign | -0.96 | Destabilizing | 0.356 | N | 0.383 | 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.