Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21329 | 64210;64211;64212 | chr2:178587226;178587225;178587224 | chr2:179451953;179451952;179451951 |
| N2AB | 19688 | 59287;59288;59289 | chr2:178587226;178587225;178587224 | chr2:179451953;179451952;179451951 |
| N2A | 18761 | 56506;56507;56508 | chr2:178587226;178587225;178587224 | chr2:179451953;179451952;179451951 |
| N2B | 12264 | 37015;37016;37017 | chr2:178587226;178587225;178587224 | chr2:179451953;179451952;179451951 |
| Novex-1 | 12389 | 37390;37391;37392 | chr2:178587226;178587225;178587224 | chr2:179451953;179451952;179451951 |
| Novex-2 | 12456 | 37591;37592;37593 | chr2:178587226;178587225;178587224 | chr2:179451953;179451952;179451951 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs754342548  |
0.211 | 0.944 | N | 0.521 | 0.205 | 0.224531998449 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 4.45E-05 | 0 |
| N/S | rs754342548 |
0.211 | 0.944 | N | 0.521 | 0.205 | 0.224531998449 | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | N | None | 2.41E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 7.36E-05 | 0 | 0 |
| N/S | rs754342548 |
0.211 | 0.944 | N | 0.521 | 0.205 | 0.224531998449 | gnomAD-4.0.0 | 1.73578E-05 | None | None | None | None | N | None | 2.67222E-05 | 1.66834E-05 | None | 0 | 0 | None | 3.12383E-05 | 0 | 1.44132E-05 | 1.09803E-05 | 8.01E-05 |
| N/T | rs754342548 |
None | 0.892 | N | 0.596 | 0.311 | 0.298403945805 | gnomAD-4.0.0 | 6.84404E-07 | None | None | None | None | N | None | 2.99097E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.1495 | likely_benign | 0.1608 | benign | -0.129 | Destabilizing | 0.916 | D | 0.565 | neutral | None | None | None | None | N |
| N/C | 0.2509 | likely_benign | 0.2697 | benign | 0.288 | Stabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| N/D | 0.1234 | likely_benign | 0.1207 | benign | 0.183 | Stabilizing | 0.981 | D | 0.57 | neutral | N | 0.472666367 | None | None | N |
| N/E | 0.3662 | ambiguous | 0.3784 | ambiguous | 0.125 | Stabilizing | 0.996 | D | 0.623 | neutral | None | None | None | None | N |
| N/F | 0.5239 | ambiguous | 0.5441 | ambiguous | -0.676 | Destabilizing | 0.975 | D | 0.691 | prob.neutral | None | None | None | None | N |
| N/G | 0.1462 | likely_benign | 0.153 | benign | -0.242 | Destabilizing | 0.957 | D | 0.529 | neutral | None | None | None | None | N |
| N/H | 0.1137 | likely_benign | 0.1179 | benign | -0.268 | Destabilizing | 0.994 | D | 0.634 | neutral | N | 0.479584765 | None | None | N |
| N/I | 0.321 | likely_benign | 0.353 | ambiguous | 0.069 | Stabilizing | 0.056 | N | 0.458 | neutral | N | 0.494183527 | None | None | N |
| N/K | 0.3599 | ambiguous | 0.3678 | ambiguous | 0.192 | Stabilizing | 0.983 | D | 0.637 | neutral | N | 0.465935183 | None | None | N |
| N/L | 0.2415 | likely_benign | 0.2599 | benign | 0.069 | Stabilizing | 0.653 | D | 0.573 | neutral | None | None | None | None | N |
| N/M | 0.3253 | likely_benign | 0.3465 | ambiguous | 0.234 | Stabilizing | 0.993 | D | 0.637 | neutral | None | None | None | None | N |
| N/P | 0.5179 | ambiguous | 0.5434 | ambiguous | 0.027 | Stabilizing | 0.996 | D | 0.644 | neutral | None | None | None | None | N |
| N/Q | 0.2984 | likely_benign | 0.311 | benign | -0.186 | Destabilizing | 0.996 | D | 0.619 | neutral | None | None | None | None | N |
| N/R | 0.4144 | ambiguous | 0.411 | ambiguous | 0.253 | Stabilizing | 0.996 | D | 0.632 | neutral | None | None | None | None | N |
| N/S | 0.0688 | likely_benign | 0.0693 | benign | 0.033 | Stabilizing | 0.944 | D | 0.521 | neutral | N | 0.512899624 | None | None | N |
| N/T | 0.1263 | likely_benign | 0.1314 | benign | 0.097 | Stabilizing | 0.892 | D | 0.596 | neutral | N | 0.483952858 | None | None | N |
| N/V | 0.2539 | likely_benign | 0.2798 | benign | 0.027 | Stabilizing | 0.653 | D | 0.583 | neutral | None | None | None | None | N |
| N/W | 0.7376 | likely_pathogenic | 0.7366 | pathogenic | -0.768 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| N/Y | 0.2005 | likely_benign | 0.2038 | benign | -0.452 | Destabilizing | 0.983 | D | 0.651 | neutral | N | 0.493930038 | 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.