Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24385 | 73378;73379;73380 | chr2:178572979;178572978;178572977 | chr2:179437706;179437705;179437704 |
| N2AB | 22744 | 68455;68456;68457 | chr2:178572979;178572978;178572977 | chr2:179437706;179437705;179437704 |
| N2A | 21817 | 65674;65675;65676 | chr2:178572979;178572978;178572977 | chr2:179437706;179437705;179437704 |
| N2B | 15320 | 46183;46184;46185 | chr2:178572979;178572978;178572977 | chr2:179437706;179437705;179437704 |
| Novex-1 | 15445 | 46558;46559;46560 | chr2:178572979;178572978;178572977 | chr2:179437706;179437705;179437704 |
| Novex-2 | 15512 | 46759;46760;46761 | chr2:178572979;178572978;178572977 | chr2:179437706;179437705;179437704 |
| 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/A | rs1403922674  |
-0.765 | 0.025 | N | 0.281 | 0.253 | 0.294206760003 | gnomAD-2.1.1 | 1.08E-05 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| T/A | rs1403922674 |
-0.765 | 0.025 | N | 0.281 | 0.253 | 0.294206760003 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| T/A | rs1403922674 |
-0.765 | 0.025 | N | 0.281 | 0.253 | 0.294206760003 | gnomAD-4.0.0 | 5.57937E-06 | None | None | None | None | N | None | 1.33501E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.78243E-06 | 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 | 0.1154 | likely_benign | 0.1177 | benign | -0.792 | Destabilizing | 0.025 | N | 0.281 | neutral | N | 0.496317257 | None | None | N |
| T/C | 0.386 | ambiguous | 0.3798 | ambiguous | -0.472 | Destabilizing | 0.997 | D | 0.646 | neutral | None | None | None | None | N |
| T/D | 0.5569 | ambiguous | 0.5748 | pathogenic | 0.594 | Stabilizing | 0.845 | D | 0.558 | neutral | None | None | None | None | N |
| T/E | 0.3519 | ambiguous | 0.3617 | ambiguous | 0.578 | Stabilizing | 0.073 | N | 0.344 | neutral | None | None | None | None | N |
| T/F | 0.3844 | ambiguous | 0.3899 | ambiguous | -1.098 | Destabilizing | 0.987 | D | 0.731 | prob.delet. | None | None | None | None | N |
| T/G | 0.4195 | ambiguous | 0.4397 | ambiguous | -0.993 | Destabilizing | 0.845 | D | 0.597 | neutral | None | None | None | None | N |
| T/H | 0.2999 | likely_benign | 0.314 | benign | -1.226 | Destabilizing | 0.997 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/I | 0.1503 | likely_benign | 0.1472 | benign | -0.36 | Destabilizing | 0.967 | D | 0.653 | neutral | N | 0.494658189 | None | None | N |
| T/K | 0.2443 | likely_benign | 0.2618 | benign | -0.32 | Destabilizing | 0.845 | D | 0.564 | neutral | None | None | None | None | N |
| T/L | 0.1206 | likely_benign | 0.1209 | benign | -0.36 | Destabilizing | 0.845 | D | 0.521 | neutral | None | None | None | None | N |
| T/M | 0.1013 | likely_benign | 0.1014 | benign | -0.199 | Destabilizing | 0.999 | D | 0.638 | neutral | None | None | None | None | N |
| T/N | 0.1706 | likely_benign | 0.1853 | benign | -0.25 | Destabilizing | 0.967 | D | 0.505 | neutral | N | 0.494658189 | None | None | N |
| T/P | 0.2924 | likely_benign | 0.3193 | benign | -0.474 | Destabilizing | 0.983 | D | 0.653 | neutral | N | 0.506547926 | None | None | N |
| T/Q | 0.2304 | likely_benign | 0.2434 | benign | -0.371 | Destabilizing | 0.95 | D | 0.649 | neutral | None | None | None | None | N |
| T/R | 0.2117 | likely_benign | 0.225 | benign | -0.178 | Destabilizing | 0.975 | D | 0.653 | neutral | None | None | None | None | N |
| T/S | 0.155 | likely_benign | 0.1671 | benign | -0.625 | Destabilizing | 0.805 | D | 0.463 | neutral | N | 0.476224765 | None | None | N |
| T/V | 0.1084 | likely_benign | 0.1059 | benign | -0.474 | Destabilizing | 0.845 | D | 0.417 | neutral | None | None | None | None | N |
| T/W | 0.7731 | likely_pathogenic | 0.7829 | pathogenic | -1.014 | Destabilizing | 0.999 | D | 0.692 | prob.neutral | None | None | None | None | N |
| T/Y | 0.42 | ambiguous | 0.438 | ambiguous | -0.753 | Destabilizing | 0.996 | D | 0.733 | prob.delet. | 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.