Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23580 | 70963;70964;70965 | chr2:178575394;178575393;178575392 | chr2:179440121;179440120;179440119 |
| N2AB | 21939 | 66040;66041;66042 | chr2:178575394;178575393;178575392 | chr2:179440121;179440120;179440119 |
| N2A | 21012 | 63259;63260;63261 | chr2:178575394;178575393;178575392 | chr2:179440121;179440120;179440119 |
| N2B | 14515 | 43768;43769;43770 | chr2:178575394;178575393;178575392 | chr2:179440121;179440120;179440119 |
| Novex-1 | 14640 | 44143;44144;44145 | chr2:178575394;178575393;178575392 | chr2:179440121;179440120;179440119 |
| Novex-2 | 14707 | 44344;44345;44346 | chr2:178575394;178575393;178575392 | chr2:179440121;179440120;179440119 |
| 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/I | rs779765346  |
None | 0.003 | N | 0.209 | 0.102 | 0.242244723065 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/I | rs779765346 |
None | 0.003 | N | 0.209 | 0.102 | 0.242244723065 | gnomAD-4.0.0 | 6.5741E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47059E-05 | 0 | 0 |
| T/S | rs779765346 |
-0.702 | 0.166 | N | 0.252 | 0.06 | 0.170165803431 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| T/S | rs779765346 |
-0.702 | 0.166 | N | 0.252 | 0.06 | 0.170165803431 | gnomAD-4.0.0 | 1.36861E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.61919E-05 | 0 | 3.31367E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0848 | likely_benign | 0.0811 | benign | -0.651 | Destabilizing | 0.001 | N | 0.088 | neutral | N | 0.492505709 | None | None | N |
| T/C | 0.353 | ambiguous | 0.3564 | ambiguous | -0.448 | Destabilizing | 0.965 | D | 0.344 | neutral | None | None | None | None | N |
| T/D | 0.4195 | ambiguous | 0.4104 | ambiguous | 0.243 | Stabilizing | 0.901 | D | 0.381 | neutral | None | None | None | None | N |
| T/E | 0.3059 | likely_benign | 0.3043 | benign | 0.228 | Stabilizing | 0.561 | D | 0.348 | neutral | None | None | None | None | N |
| T/F | 0.2428 | likely_benign | 0.2271 | benign | -0.799 | Destabilizing | 0.818 | D | 0.381 | neutral | None | None | None | None | N |
| T/G | 0.2311 | likely_benign | 0.2217 | benign | -0.877 | Destabilizing | 0.39 | N | 0.302 | neutral | None | None | None | None | N |
| T/H | 0.2203 | likely_benign | 0.2125 | benign | -1.054 | Destabilizing | 0.991 | D | 0.344 | neutral | None | None | None | None | N |
| T/I | 0.1395 | likely_benign | 0.1332 | benign | -0.153 | Destabilizing | 0.003 | N | 0.209 | neutral | N | 0.490870913 | None | None | N |
| T/K | 0.2307 | likely_benign | 0.2282 | benign | -0.55 | Destabilizing | 0.561 | D | 0.35 | neutral | None | None | None | None | N |
| T/L | 0.0912 | likely_benign | 0.0871 | benign | -0.153 | Destabilizing | 0.002 | N | 0.136 | neutral | None | None | None | None | N |
| T/M | 0.0843 | likely_benign | 0.0812 | benign | -0.067 | Destabilizing | 0.818 | D | 0.363 | neutral | None | None | None | None | N |
| T/N | 0.1066 | likely_benign | 0.1004 | benign | -0.465 | Destabilizing | 0.873 | D | 0.337 | neutral | N | 0.52117239 | None | None | N |
| T/P | 0.5313 | ambiguous | 0.4998 | ambiguous | -0.287 | Destabilizing | 0.873 | D | 0.385 | neutral | N | 0.491461276 | None | None | N |
| T/Q | 0.2011 | likely_benign | 0.195 | benign | -0.597 | Destabilizing | 0.901 | D | 0.368 | neutral | None | None | None | None | N |
| T/R | 0.2011 | likely_benign | 0.1983 | benign | -0.309 | Destabilizing | 0.901 | D | 0.387 | neutral | None | None | None | None | N |
| T/S | 0.0975 | likely_benign | 0.0919 | benign | -0.767 | Destabilizing | 0.166 | N | 0.252 | neutral | N | 0.439692731 | None | None | N |
| T/V | 0.1127 | likely_benign | 0.1096 | benign | -0.287 | Destabilizing | 0.007 | N | 0.087 | neutral | None | None | None | None | N |
| T/W | 0.5992 | likely_pathogenic | 0.5852 | pathogenic | -0.757 | Destabilizing | 0.991 | D | 0.39 | neutral | None | None | None | None | N |
| T/Y | 0.2786 | likely_benign | 0.2665 | benign | -0.511 | Destabilizing | 0.901 | D | 0.369 | 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.