Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30741 | 92446;92447;92448 | chr2:178549405;178549404;178549403 | chr2:179414132;179414131;179414130 |
| N2AB | 29100 | 87523;87524;87525 | chr2:178549405;178549404;178549403 | chr2:179414132;179414131;179414130 |
| N2A | 28173 | 84742;84743;84744 | chr2:178549405;178549404;178549403 | chr2:179414132;179414131;179414130 |
| N2B | 21676 | 65251;65252;65253 | chr2:178549405;178549404;178549403 | chr2:179414132;179414131;179414130 |
| Novex-1 | 21801 | 65626;65627;65628 | chr2:178549405;178549404;178549403 | chr2:179414132;179414131;179414130 |
| Novex-2 | 21868 | 65827;65828;65829 | chr2:178549405;178549404;178549403 | chr2:179414132;179414131;179414130 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/V | rs202090888  |
-0.166 | 0.062 | N | 0.369 | 0.146 | None | gnomAD-2.1.1 | 3.58E-05 | None | None | None | None | N | None | 0 | 5.66E-05 | None | 0 | 0 | None | 0 | None | 0 | 6.27E-05 | 0 |
| A/V | rs202090888 |
-0.166 | 0.062 | N | 0.369 | 0.146 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.82E-05 | 0 | 0 |
| A/V | rs202090888 |
-0.166 | 0.062 | N | 0.369 | 0.146 | None | gnomAD-4.0.0 | 5.08192E-05 | None | None | None | None | N | None | 0 | 5.00133E-05 | None | 0 | 0 | None | 0 | 1.64474E-04 | 6.18778E-05 | 0 | 8.00615E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.2988 | likely_benign | 0.3266 | benign | -0.842 | Destabilizing | 0.824 | D | 0.43 | neutral | None | None | None | None | N |
| A/D | 0.177 | likely_benign | 0.1912 | benign | -0.823 | Destabilizing | 0.081 | N | 0.511 | neutral | None | None | None | None | N |
| A/E | 0.1437 | likely_benign | 0.1555 | benign | -0.861 | Destabilizing | None | N | 0.276 | neutral | N | 0.405038653 | None | None | N |
| A/F | 0.2364 | likely_benign | 0.2546 | benign | -0.913 | Destabilizing | 0.555 | D | 0.613 | neutral | None | None | None | None | N |
| A/G | 0.098 | likely_benign | 0.1007 | benign | -1.013 | Destabilizing | 0.117 | N | 0.372 | neutral | N | 0.454315467 | None | None | N |
| A/H | 0.2863 | likely_benign | 0.3 | benign | -1.091 | Destabilizing | 0.824 | D | 0.581 | neutral | None | None | None | None | N |
| A/I | 0.1554 | likely_benign | 0.1658 | benign | -0.271 | Destabilizing | 0.235 | N | 0.561 | neutral | None | None | None | None | N |
| A/K | 0.2362 | likely_benign | 0.2505 | benign | -1.072 | Destabilizing | 0.081 | N | 0.435 | neutral | None | None | None | None | N |
| A/L | 0.1025 | likely_benign | 0.103 | benign | -0.271 | Destabilizing | 0.081 | N | 0.441 | neutral | None | None | None | None | N |
| A/M | 0.1305 | likely_benign | 0.1369 | benign | -0.308 | Destabilizing | 0.824 | D | 0.5 | neutral | None | None | None | None | N |
| A/N | 0.1255 | likely_benign | 0.134 | benign | -0.784 | Destabilizing | 0.149 | N | 0.609 | neutral | None | None | None | None | N |
| A/P | 0.2289 | likely_benign | 0.2621 | benign | -0.396 | Destabilizing | 0.484 | N | 0.559 | neutral | N | 0.4933725 | None | None | N |
| A/Q | 0.186 | likely_benign | 0.1947 | benign | -0.923 | Destabilizing | 0.235 | N | 0.553 | neutral | None | None | None | None | N |
| A/R | 0.2353 | likely_benign | 0.2517 | benign | -0.723 | Destabilizing | 0.38 | N | 0.56 | neutral | None | None | None | None | N |
| A/S | 0.076 | likely_benign | 0.0767 | benign | -1.141 | Destabilizing | 0.005 | N | 0.207 | neutral | N | 0.408193601 | None | None | N |
| A/T | 0.0648 | likely_benign | 0.0654 | benign | -1.072 | Destabilizing | None | N | 0.167 | neutral | N | 0.390666633 | None | None | N |
| A/V | 0.0971 | likely_benign | 0.1005 | benign | -0.396 | Destabilizing | 0.062 | N | 0.369 | neutral | N | 0.501010549 | None | None | N |
| A/W | 0.5536 | ambiguous | 0.5817 | pathogenic | -1.22 | Destabilizing | 0.935 | D | 0.694 | prob.neutral | None | None | None | None | N |
| A/Y | 0.3055 | likely_benign | 0.3295 | benign | -0.812 | Destabilizing | 0.555 | D | 0.597 | 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.