Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19955 | 60088;60089;60090 | chr2:178592041;178592040;178592039 | chr2:179456768;179456767;179456766 |
| N2AB | 18314 | 55165;55166;55167 | chr2:178592041;178592040;178592039 | chr2:179456768;179456767;179456766 |
| N2A | 17387 | 52384;52385;52386 | chr2:178592041;178592040;178592039 | chr2:179456768;179456767;179456766 |
| N2B | 10890 | 32893;32894;32895 | chr2:178592041;178592040;178592039 | chr2:179456768;179456767;179456766 |
| Novex-1 | 11015 | 33268;33269;33270 | chr2:178592041;178592040;178592039 | chr2:179456768;179456767;179456766 |
| Novex-2 | 11082 | 33469;33470;33471 | chr2:178592041;178592040;178592039 | chr2:179456768;179456767;179456766 |
| 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/I | None | None | 0.999 | D | 0.802 | 0.575 | 0.793078964774 |
Yu (2019) 
| None |
Other 
|
comp het with L30639P (in trans), c.44282-2A>G (in cis) | None | None | N | Genetic analysis of single patient with congenital titinopathy; comp het with L30639P; significant decrease in full-length titin protein in biopsy samples compared to WT | None | None | None | None | None | None | None | None | None | None | None |
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 | 0.9996 | likely_pathogenic | 0.9995 | pathogenic | -0.812 | Destabilizing | 0.994 | D | 0.683 | prob.neutral | None | None | None | None | N |
| N/C | 0.9938 | likely_pathogenic | 0.9943 | pathogenic | -0.929 | Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| N/D | 0.9948 | likely_pathogenic | 0.9948 | pathogenic | -2.495 | Highly Destabilizing | 0.996 | D | 0.577 | neutral | D | 0.524665408 | None | None | N |
| N/E | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -2.305 | Highly Destabilizing | 0.997 | D | 0.633 | neutral | None | None | None | None | N |
| N/F | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -0.837 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| N/G | 0.9976 | likely_pathogenic | 0.9973 | pathogenic | -1.055 | Destabilizing | 0.997 | D | 0.561 | neutral | None | None | None | None | N |
| N/H | 0.9956 | likely_pathogenic | 0.9958 | pathogenic | -0.818 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | D | 0.552937881 | None | None | N |
| N/I | 0.9984 | likely_pathogenic | 0.9986 | pathogenic | -0.2 | Destabilizing | 0.999 | D | 0.802 | deleterious | D | 0.55319137 | None | None | N |
| N/K | 0.9993 | likely_pathogenic | 0.9993 | pathogenic | -0.336 | Destabilizing | 0.996 | D | 0.649 | neutral | D | 0.551923923 | None | None | N |
| N/L | 0.9965 | likely_pathogenic | 0.9971 | pathogenic | -0.2 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| N/M | 0.9977 | likely_pathogenic | 0.9981 | pathogenic | -0.257 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| N/P | 0.9998 | likely_pathogenic | 0.9997 | pathogenic | -0.382 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| N/Q | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -1.084 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| N/R | 0.9992 | likely_pathogenic | 0.9992 | pathogenic | -0.385 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| N/S | 0.9827 | likely_pathogenic | 0.9834 | pathogenic | -1.115 | Destabilizing | 0.905 | D | 0.335 | neutral | N | 0.50176176 | None | None | N |
| N/T | 0.9912 | likely_pathogenic | 0.9921 | pathogenic | -0.81 | Destabilizing | 0.992 | D | 0.591 | neutral | N | 0.499226865 | None | None | N |
| N/V | 0.9984 | likely_pathogenic | 0.9985 | pathogenic | -0.382 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| N/W | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -1.044 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| N/Y | 0.9976 | likely_pathogenic | 0.9975 | pathogenic | -0.548 | Destabilizing | 1.0 | D | 0.799 | deleterious | D | 0.552937881 | 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.