Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23001 | 69226;69227;69228 | chr2:178577334;178577333;178577332 | chr2:179442061;179442060;179442059 |
| N2AB | 21360 | 64303;64304;64305 | chr2:178577334;178577333;178577332 | chr2:179442061;179442060;179442059 |
| N2A | 20433 | 61522;61523;61524 | chr2:178577334;178577333;178577332 | chr2:179442061;179442060;179442059 |
| N2B | 13936 | 42031;42032;42033 | chr2:178577334;178577333;178577332 | chr2:179442061;179442060;179442059 |
| Novex-1 | 14061 | 42406;42407;42408 | chr2:178577334;178577333;178577332 | chr2:179442061;179442060;179442059 |
| Novex-2 | 14128 | 42607;42608;42609 | chr2:178577334;178577333;178577332 | chr2:179442061;179442060;179442059 |
| 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 | rs1215862556  |
-0.402 | 1.0 | N | 0.766 | 0.457 | 0.584891512018 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs1215862556 |
-0.402 | 1.0 | N | 0.766 | 0.457 | 0.584891512018 | gnomAD-4.0.0 | 2.7374E-06 | None | None | None | None | N | None | 2.98972E-05 | 4.47287E-05 | None | 0 | 2.52449E-05 | 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 | 0.0801 | likely_benign | 0.0806 | benign | -0.656 | Destabilizing | 0.999 | D | 0.617 | neutral | N | 0.481841215 | None | None | N |
| T/C | 0.4795 | ambiguous | 0.4989 | ambiguous | -0.371 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| T/D | 0.3772 | ambiguous | 0.4038 | ambiguous | 0.561 | Stabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| T/E | 0.3171 | likely_benign | 0.3325 | benign | 0.507 | Stabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| T/F | 0.2539 | likely_benign | 0.2523 | benign | -1.086 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| T/G | 0.2073 | likely_benign | 0.2067 | benign | -0.806 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| T/H | 0.2503 | likely_benign | 0.2578 | benign | -1.13 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| T/I | 0.2327 | likely_benign | 0.2392 | benign | -0.371 | Destabilizing | 1.0 | D | 0.766 | deleterious | N | 0.490163008 | None | None | N |
| T/K | 0.199 | likely_benign | 0.2007 | benign | -0.298 | Destabilizing | 1.0 | D | 0.782 | deleterious | N | 0.492402213 | None | None | N |
| T/L | 0.1177 | likely_benign | 0.1194 | benign | -0.371 | Destabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | N |
| T/M | 0.1131 | likely_benign | 0.112 | benign | -0.116 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| T/N | 0.1216 | likely_benign | 0.1315 | benign | -0.128 | Destabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | N |
| T/P | 0.3666 | ambiguous | 0.3942 | ambiguous | -0.437 | Destabilizing | 1.0 | D | 0.758 | deleterious | N | 0.520610322 | None | None | N |
| T/Q | 0.2135 | likely_benign | 0.2231 | benign | -0.33 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| T/R | 0.1694 | likely_benign | 0.1757 | benign | -0.12 | Destabilizing | 1.0 | D | 0.759 | deleterious | N | 0.488767262 | None | None | N |
| T/S | 0.0991 | likely_benign | 0.1012 | benign | -0.46 | Destabilizing | 0.999 | D | 0.634 | neutral | N | 0.468237274 | None | None | N |
| T/V | 0.1761 | likely_benign | 0.1758 | benign | -0.437 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| T/W | 0.6438 | likely_pathogenic | 0.6631 | pathogenic | -1.011 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| T/Y | 0.2373 | likely_benign | 0.2461 | benign | -0.751 | Destabilizing | 1.0 | D | 0.77 | deleterious | 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.