Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30954 | 93085;93086;93087 | chr2:178548766;178548765;178548764 | chr2:179413493;179413492;179413491 |
| N2AB | 29313 | 88162;88163;88164 | chr2:178548766;178548765;178548764 | chr2:179413493;179413492;179413491 |
| N2A | 28386 | 85381;85382;85383 | chr2:178548766;178548765;178548764 | chr2:179413493;179413492;179413491 |
| N2B | 21889 | 65890;65891;65892 | chr2:178548766;178548765;178548764 | chr2:179413493;179413492;179413491 |
| Novex-1 | 22014 | 66265;66266;66267 | chr2:178548766;178548765;178548764 | chr2:179413493;179413492;179413491 |
| Novex-2 | 22081 | 66466;66467;66468 | chr2:178548766;178548765;178548764 | chr2:179413493;179413492;179413491 |
| 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 | rs72648248  |
-0.279 | 0.009 | N | 0.312 | 0.109 | 0.251639045875 | gnomAD-2.1.1 | 3.93E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.56437E-04 | None | 0 | None | 0 | 4.68E-05 | 0 |
| T/I | rs72648248 |
-0.279 | 0.009 | N | 0.312 | 0.109 | 0.251639045875 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92753E-04 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| T/I | rs72648248 |
-0.279 | 0.009 | N | 0.312 | 0.109 | 0.251639045875 | gnomAD-4.0.0 | 2.78922E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.00553E-04 | None | 0 | 0 | 2.96658E-05 | 0 | 1.60118E-05 |
| T/S | rs778473278 |
-0.684 | 0.027 | D | 0.329 | 0.072 | 0.17948927462 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78676E-04 | None | 0 | None | 0 | 0 | 0 |
| T/S | rs778473278 |
-0.684 | 0.027 | D | 0.329 | 0.072 | 0.17948927462 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92753E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs778473278 |
-0.684 | 0.027 | D | 0.329 | 0.072 | 0.17948927462 | gnomAD-4.0.0 | 5.57886E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.00544E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0562 | likely_benign | 0.0553 | benign | -0.555 | Destabilizing | None | N | 0.196 | neutral | N | 0.43460749 | None | None | N |
| T/C | 0.3198 | likely_benign | 0.2987 | benign | -0.304 | Destabilizing | 0.824 | D | 0.374 | neutral | None | None | None | None | N |
| T/D | 0.3693 | ambiguous | 0.3489 | ambiguous | -0.077 | Destabilizing | 0.555 | D | 0.357 | neutral | None | None | None | None | N |
| T/E | 0.2446 | likely_benign | 0.2367 | benign | -0.138 | Destabilizing | 0.149 | N | 0.36 | neutral | None | None | None | None | N |
| T/F | 0.1801 | likely_benign | 0.1725 | benign | -0.848 | Destabilizing | 0.38 | N | 0.491 | neutral | None | None | None | None | N |
| T/G | 0.2284 | likely_benign | 0.2152 | benign | -0.734 | Destabilizing | 0.081 | N | 0.421 | neutral | None | None | None | None | N |
| T/H | 0.2356 | likely_benign | 0.2213 | benign | -1.064 | Destabilizing | 0.935 | D | 0.486 | neutral | None | None | None | None | N |
| T/I | 0.0706 | likely_benign | 0.0722 | benign | -0.19 | Destabilizing | 0.009 | N | 0.312 | neutral | N | 0.511145477 | None | None | N |
| T/K | 0.1649 | likely_benign | 0.1586 | benign | -0.658 | Destabilizing | 0.149 | N | 0.353 | neutral | None | None | None | None | N |
| T/L | 0.0624 | likely_benign | 0.063 | benign | -0.19 | Destabilizing | 0.035 | N | 0.346 | neutral | None | None | None | None | N |
| T/M | 0.0708 | likely_benign | 0.0709 | benign | 0.088 | Stabilizing | 0.38 | N | 0.377 | neutral | None | None | None | None | N |
| T/N | 0.1118 | likely_benign | 0.1102 | benign | -0.378 | Destabilizing | 0.484 | N | 0.349 | neutral | N | 0.489758161 | None | None | N |
| T/P | 0.0698 | likely_benign | 0.067 | benign | -0.282 | Destabilizing | 0.484 | N | 0.371 | neutral | N | 0.452558533 | None | None | N |
| T/Q | 0.1784 | likely_benign | 0.1688 | benign | -0.628 | Destabilizing | 0.555 | D | 0.379 | neutral | None | None | None | None | N |
| T/R | 0.1626 | likely_benign | 0.1598 | benign | -0.36 | Destabilizing | 0.38 | N | 0.385 | neutral | None | None | None | None | N |
| T/S | 0.0998 | likely_benign | 0.0953 | benign | -0.604 | Destabilizing | 0.027 | N | 0.329 | neutral | D | 0.524477346 | None | None | N |
| T/V | 0.0604 | likely_benign | 0.0625 | benign | -0.282 | Destabilizing | None | N | 0.195 | neutral | None | None | None | None | N |
| T/W | 0.5839 | likely_pathogenic | 0.561 | ambiguous | -0.807 | Destabilizing | 0.935 | D | 0.533 | neutral | None | None | None | None | N |
| T/Y | 0.2513 | likely_benign | 0.2434 | benign | -0.576 | Destabilizing | 0.555 | D | 0.487 | 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.