TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34336	103231;103232;103233	chr2:178533609;178533608;178533607	chr2:179398336;179398335;179398334
N2AB	32695	98308;98309;98310	chr2:178533609;178533608;178533607	chr2:179398336;179398335;179398334
N2A	31768	95527;95528;95529	chr2:178533609;178533608;178533607	chr2:179398336;179398335;179398334
N2B	25271	76036;76037;76038	chr2:178533609;178533608;178533607	chr2:179398336;179398335;179398334
Novex-1	25396	76411;76412;76413	chr2:178533609;178533608;178533607	chr2:179398336;179398335;179398334
Novex-2	25463	76612;76613;76614	chr2:178533609;178533608;178533607	chr2:179398336;179398335;179398334
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-161
• Domain position: 79
• Structural Position: 159
• Q(SASA): 0.6691
• Predicted PPI site: I

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
R/K	None	None	None	N	0.127	0.058	0.162503812791	gnomAD-4.0.0	1.36832E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79882E-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
R/A	0.4589	ambiguous	0.5127	ambiguous	-0.383	Destabilizing	0.055	N	0.438	neutral	None	None	None	None	I
R/C	0.2193	likely_benign	0.223	benign	-0.29	Destabilizing	0.958	D	0.458	neutral	None	None	None	None	I
R/D	0.8239	likely_pathogenic	0.8315	pathogenic	0.03	Stabilizing	0.22	N	0.522	neutral	None	None	None	None	I
R/E	0.3838	ambiguous	0.4271	ambiguous	0.135	Stabilizing	0.055	N	0.395	neutral	None	None	None	None	I
R/F	0.6783	likely_pathogenic	0.7299	pathogenic	-0.318	Destabilizing	0.667	D	0.481	neutral	None	None	None	None	I
R/G	0.3728	ambiguous	0.4238	ambiguous	-0.673	Destabilizing	0.175	N	0.483	neutral	N	0.477512906	None	None	I
R/H	0.1249	likely_benign	0.1174	benign	-1.103	Destabilizing	0.001	N	0.157	neutral	None	None	None	None	I
R/I	0.3789	ambiguous	0.4232	ambiguous	0.381	Stabilizing	0.124	N	0.548	neutral	None	None	None	None	I
R/K	0.077	likely_benign	0.0954	benign	-0.421	Destabilizing	None	N	0.127	neutral	N	0.403975152	None	None	I
R/L	0.372	ambiguous	0.4134	ambiguous	0.381	Stabilizing	0.055	N	0.485	neutral	None	None	None	None	I
R/M	0.3188	likely_benign	0.4124	ambiguous	0.028	Stabilizing	0.602	D	0.478	neutral	N	0.495367948	None	None	I
R/N	0.6287	likely_pathogenic	0.6662	pathogenic	0.082	Stabilizing	0.22	N	0.4	neutral	None	None	None	None	I
R/P	0.9777	likely_pathogenic	0.9831	pathogenic	0.148	Stabilizing	0.364	N	0.488	neutral	None	None	None	None	I
R/Q	0.1064	likely_benign	0.1137	benign	-0.071	Destabilizing	0.011	N	0.201	neutral	None	None	None	None	I
R/S	0.4939	ambiguous	0.5233	ambiguous	-0.529	Destabilizing	0.042	N	0.449	neutral	N	0.44103203	None	None	I
R/T	0.238	likely_benign	0.2716	benign	-0.253	Destabilizing	0.175	N	0.463	neutral	N	0.431217682	None	None	I
R/V	0.3972	ambiguous	0.459	ambiguous	0.148	Stabilizing	0.001	N	0.31	neutral	None	None	None	None	I
R/W	0.2694	likely_benign	0.2796	benign	-0.106	Destabilizing	0.946	D	0.469	neutral	D	0.52732565	None	None	I
R/Y	0.5452	ambiguous	0.5693	pathogenic	0.23	Stabilizing	0.497	N	0.487	neutral	None	None	None	None	I

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.