Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21829 | 65710;65711;65712 | chr2:178583697;178583696;178583695 | chr2:179448424;179448423;179448422 |
| N2AB | 20188 | 60787;60788;60789 | chr2:178583697;178583696;178583695 | chr2:179448424;179448423;179448422 |
| N2A | 19261 | 58006;58007;58008 | chr2:178583697;178583696;178583695 | chr2:179448424;179448423;179448422 |
| N2B | 12764 | 38515;38516;38517 | chr2:178583697;178583696;178583695 | chr2:179448424;179448423;179448422 |
| Novex-1 | 12889 | 38890;38891;38892 | chr2:178583697;178583696;178583695 | chr2:179448424;179448423;179448422 |
| Novex-2 | 12956 | 39091;39092;39093 | chr2:178583697;178583696;178583695 | chr2:179448424;179448423;179448422 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/E | None | None | 0.349 | N | 0.392 | 0.205 | 0.158396225186 | gnomAD-4.0.0 | 1.36967E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79982E-06 | 0 | 0 |
| Q/R | rs886038921  |
-0.124 | 0.008 | N | 0.235 | 0.215 | 0.112648838833 | gnomAD-2.1.1 | 8.09E-06 | None | None | None | None | N | None | 0 | 5.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Q/R | rs886038921 |
-0.124 | 0.008 | N | 0.235 | 0.215 | 0.112648838833 | gnomAD-4.0.0 | 3.18916E-06 | None | None | None | None | N | None | 0 | 4.58127E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.2169 | likely_benign | 0.1809 | benign | -0.735 | Destabilizing | 0.587 | D | 0.464 | neutral | None | None | None | None | N |
| Q/C | 0.6696 | likely_pathogenic | 0.5599 | ambiguous | -0.102 | Destabilizing | 0.996 | D | 0.767 | deleterious | None | None | None | None | N |
| Q/D | 0.5098 | ambiguous | 0.417 | ambiguous | -0.642 | Destabilizing | 0.775 | D | 0.491 | neutral | None | None | None | None | N |
| Q/E | 0.0969 | likely_benign | 0.0864 | benign | -0.457 | Destabilizing | 0.349 | N | 0.392 | neutral | N | 0.380316354 | None | None | N |
| Q/F | 0.7805 | likely_pathogenic | 0.6808 | pathogenic | -0.188 | Destabilizing | 0.987 | D | 0.761 | deleterious | None | None | None | None | N |
| Q/G | 0.384 | ambiguous | 0.3121 | benign | -1.161 | Destabilizing | 0.775 | D | 0.589 | neutral | None | None | None | None | N |
| Q/H | 0.338 | likely_benign | 0.2511 | benign | -0.758 | Destabilizing | 0.949 | D | 0.573 | neutral | N | 0.514902566 | None | None | N |
| Q/I | 0.3569 | ambiguous | 0.2876 | benign | 0.394 | Stabilizing | 0.961 | D | 0.757 | deleterious | None | None | None | None | N |
| Q/K | 0.11 | likely_benign | 0.09 | benign | -0.262 | Destabilizing | 0.008 | N | 0.153 | neutral | N | 0.445386552 | None | None | N |
| Q/L | 0.1803 | likely_benign | 0.1415 | benign | 0.394 | Stabilizing | 0.722 | D | 0.589 | neutral | N | 0.484753017 | None | None | N |
| Q/M | 0.3764 | ambiguous | 0.3164 | benign | 0.658 | Stabilizing | 0.987 | D | 0.573 | neutral | None | None | None | None | N |
| Q/N | 0.4006 | ambiguous | 0.3212 | benign | -0.962 | Destabilizing | 0.775 | D | 0.507 | neutral | None | None | None | None | N |
| Q/P | 0.2013 | likely_benign | 0.1666 | benign | 0.048 | Stabilizing | 0.949 | D | 0.637 | neutral | N | 0.492564424 | None | None | N |
| Q/R | 0.1177 | likely_benign | 0.1005 | benign | -0.304 | Destabilizing | 0.008 | N | 0.235 | neutral | N | 0.438788654 | None | None | N |
| Q/S | 0.2516 | likely_benign | 0.2105 | benign | -1.176 | Destabilizing | 0.775 | D | 0.443 | neutral | None | None | None | None | N |
| Q/T | 0.1627 | likely_benign | 0.1368 | benign | -0.779 | Destabilizing | 0.775 | D | 0.563 | neutral | None | None | None | None | N |
| Q/V | 0.2083 | likely_benign | 0.1721 | benign | 0.048 | Stabilizing | 0.961 | D | 0.665 | neutral | None | None | None | None | N |
| Q/W | 0.6696 | likely_pathogenic | 0.582 | pathogenic | -0.076 | Destabilizing | 0.996 | D | 0.765 | deleterious | None | None | None | None | N |
| Q/Y | 0.6217 | likely_pathogenic | 0.509 | ambiguous | 0.194 | Stabilizing | 0.987 | D | 0.685 | prob.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.