Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23004 | 69235;69236;69237 | chr2:178577325;178577324;178577323 | chr2:179442052;179442051;179442050 |
| N2AB | 21363 | 64312;64313;64314 | chr2:178577325;178577324;178577323 | chr2:179442052;179442051;179442050 |
| N2A | 20436 | 61531;61532;61533 | chr2:178577325;178577324;178577323 | chr2:179442052;179442051;179442050 |
| N2B | 13939 | 42040;42041;42042 | chr2:178577325;178577324;178577323 | chr2:179442052;179442051;179442050 |
| Novex-1 | 14064 | 42415;42416;42417 | chr2:178577325;178577324;178577323 | chr2:179442052;179442051;179442050 |
| Novex-2 | 14131 | 42616;42617;42618 | chr2:178577325;178577324;178577323 | chr2:179442052;179442051;179442050 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/R | None | None | None | N | 0.188 | 0.344 | 0.315903272564 | gnomAD-4.0.0 | 1.59207E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85969E-06 | 0 | 0 |
| M/V | rs1257560836  |
-0.513 | None | N | 0.116 | 0.176 | 0.281780670237 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| M/V | rs1257560836 |
-0.513 | None | N | 0.116 | 0.176 | 0.281780670237 | gnomAD-4.0.0 | 1.36872E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99611E-07 | 1.1595E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.15 | likely_benign | 0.1464 | benign | -1.643 | Destabilizing | 0.002 | N | 0.223 | neutral | None | None | None | None | N |
| M/C | 0.427 | ambiguous | 0.417 | ambiguous | -2.042 | Highly Destabilizing | 0.245 | N | 0.487 | neutral | None | None | None | None | N |
| M/D | 0.6104 | likely_pathogenic | 0.5825 | pathogenic | -1.308 | Destabilizing | 0.018 | N | 0.381 | neutral | None | None | None | None | N |
| M/E | 0.2617 | likely_benign | 0.2546 | benign | -1.211 | Destabilizing | 0.008 | N | 0.349 | neutral | None | None | None | None | N |
| M/F | 0.2854 | likely_benign | 0.2497 | benign | -0.731 | Destabilizing | 0.044 | N | 0.4 | neutral | None | None | None | None | N |
| M/G | 0.3897 | ambiguous | 0.3688 | ambiguous | -2.009 | Highly Destabilizing | 0.008 | N | 0.381 | neutral | None | None | None | None | N |
| M/H | 0.2774 | likely_benign | 0.2528 | benign | -1.407 | Destabilizing | 0.245 | N | 0.569 | neutral | None | None | None | None | N |
| M/I | 0.1786 | likely_benign | 0.1553 | benign | -0.666 | Destabilizing | 0.001 | N | 0.31 | neutral | N | 0.402129713 | None | None | N |
| M/K | 0.118 | likely_benign | 0.1066 | benign | -0.677 | Destabilizing | 0.003 | N | 0.291 | neutral | N | 0.39760654 | None | None | N |
| M/L | 0.1116 | likely_benign | 0.1033 | benign | -0.666 | Destabilizing | 0.001 | N | 0.195 | neutral | N | 0.406900814 | None | None | N |
| M/N | 0.2478 | likely_benign | 0.2327 | benign | -0.783 | Destabilizing | 0.018 | N | 0.372 | neutral | None | None | None | None | N |
| M/P | 0.9677 | likely_pathogenic | 0.9596 | pathogenic | -0.966 | Destabilizing | 0.037 | N | 0.442 | neutral | None | None | None | None | N |
| M/Q | 0.1307 | likely_benign | 0.1305 | benign | -0.771 | Destabilizing | 0.018 | N | 0.361 | neutral | None | None | None | None | N |
| M/R | 0.1314 | likely_benign | 0.1186 | benign | -0.505 | Destabilizing | None | N | 0.188 | neutral | N | 0.392027362 | None | None | N |
| M/S | 0.1374 | likely_benign | 0.137 | benign | -1.38 | Destabilizing | None | N | 0.19 | neutral | None | None | None | None | N |
| M/T | 0.0669 | likely_benign | 0.0651 | benign | -1.161 | Destabilizing | None | N | 0.179 | neutral | N | 0.311715565 | None | None | N |
| M/V | 0.0726 | likely_benign | 0.0657 | benign | -0.966 | Destabilizing | None | N | 0.116 | neutral | N | 0.346025714 | None | None | N |
| M/W | 0.6543 | likely_pathogenic | 0.6133 | pathogenic | -0.853 | Destabilizing | 0.497 | N | 0.495 | neutral | None | None | None | None | N |
| M/Y | 0.4539 | ambiguous | 0.4245 | ambiguous | -0.733 | Destabilizing | 0.085 | N | 0.506 | 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.