Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22994 | 69205;69206;69207 | chr2:178577355;178577354;178577353 | chr2:179442082;179442081;179442080 |
| N2AB | 21353 | 64282;64283;64284 | chr2:178577355;178577354;178577353 | chr2:179442082;179442081;179442080 |
| N2A | 20426 | 61501;61502;61503 | chr2:178577355;178577354;178577353 | chr2:179442082;179442081;179442080 |
| N2B | 13929 | 42010;42011;42012 | chr2:178577355;178577354;178577353 | chr2:179442082;179442081;179442080 |
| Novex-1 | 14054 | 42385;42386;42387 | chr2:178577355;178577354;178577353 | chr2:179442082;179442081;179442080 |
| Novex-2 | 14121 | 42586;42587;42588 | chr2:178577355;178577354;178577353 | chr2:179442082;179442081;179442080 |
| 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 | rs183056142  |
0.118 | None | N | 0.274 | 0.11 | None | gnomAD-2.1.1 | 5E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 6.18876E-04 | None | 0 | None | 0 | 0 | 1.40489E-04 |
| T/I | rs183056142 |
0.118 | None | N | 0.274 | 0.11 | None | gnomAD-3.1.2 | 1.25447E-04 | None | None | None | None | N | None | 0 | 6.61E-05 | 0 | 0 | 3.50058E-03 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs183056142 |
0.118 | None | N | 0.274 | 0.11 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| T/I | rs183056142 |
0.118 | None | N | 0.274 | 0.11 | None | gnomAD-4.0.0 | 2.73443E-04 | None | None | None | None | N | None | 0 | 3.34158E-05 | None | 0 | 9.72502E-03 | None | 0 | 0 | 0 | 0 | 6.40512E-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 | 0.0793 | likely_benign | 0.0784 | benign | -1.096 | Destabilizing | None | N | 0.113 | neutral | N | 0.442264181 | None | None | N |
| T/C | 0.2288 | likely_benign | 0.1625 | benign | -0.84 | Destabilizing | None | N | 0.335 | neutral | None | None | None | None | N |
| T/D | 0.5315 | ambiguous | 0.4988 | ambiguous | -0.966 | Destabilizing | 0.009 | N | 0.574 | neutral | None | None | None | None | N |
| T/E | 0.4044 | ambiguous | 0.38 | ambiguous | -0.836 | Destabilizing | 0.009 | N | 0.546 | neutral | None | None | None | None | N |
| T/F | 0.1654 | likely_benign | 0.1336 | benign | -0.83 | Destabilizing | 0.044 | N | 0.632 | neutral | None | None | None | None | N |
| T/G | 0.2417 | likely_benign | 0.2233 | benign | -1.474 | Destabilizing | 0.004 | N | 0.496 | neutral | None | None | None | None | N |
| T/H | 0.2538 | likely_benign | 0.217 | benign | -1.695 | Destabilizing | 0.245 | N | 0.617 | neutral | None | None | None | None | N |
| T/I | 0.0846 | likely_benign | 0.0748 | benign | -0.134 | Destabilizing | None | N | 0.274 | neutral | N | 0.424542425 | None | None | N |
| T/K | 0.2814 | likely_benign | 0.2591 | benign | -0.769 | Destabilizing | 0.009 | N | 0.545 | neutral | None | None | None | None | N |
| T/L | 0.0727 | likely_benign | 0.0677 | benign | -0.134 | Destabilizing | 0.001 | N | 0.369 | neutral | None | None | None | None | N |
| T/M | 0.0799 | likely_benign | 0.0746 | benign | -0.045 | Destabilizing | 0.138 | N | 0.663 | neutral | None | None | None | None | N |
| T/N | 0.1594 | likely_benign | 0.1417 | benign | -1.15 | Destabilizing | 0.017 | N | 0.509 | neutral | N | 0.497445461 | None | None | N |
| T/P | 0.3942 | ambiguous | 0.4108 | ambiguous | -0.421 | Destabilizing | 0.033 | N | 0.606 | neutral | N | 0.516031221 | None | None | N |
| T/Q | 0.263 | likely_benign | 0.2451 | benign | -1.072 | Destabilizing | 0.044 | N | 0.633 | neutral | None | None | None | None | N |
| T/R | 0.2186 | likely_benign | 0.205 | benign | -0.837 | Destabilizing | 0.044 | N | 0.611 | neutral | None | None | None | None | N |
| T/S | 0.1114 | likely_benign | 0.099 | benign | -1.418 | Destabilizing | None | N | 0.117 | neutral | N | 0.488305902 | None | None | N |
| T/V | 0.0785 | likely_benign | 0.0687 | benign | -0.421 | Destabilizing | None | N | 0.113 | neutral | None | None | None | None | N |
| T/W | 0.486 | ambiguous | 0.4183 | ambiguous | -0.867 | Destabilizing | 0.788 | D | 0.608 | neutral | None | None | None | None | N |
| T/Y | 0.1896 | likely_benign | 0.1536 | benign | -0.559 | Destabilizing | 0.085 | N | 0.658 | 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.