TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26824	80695;80696;80697	chr2:178565662;178565661;178565660	chr2:179430389;179430388;179430387
N2AB	25183	75772;75773;75774	chr2:178565662;178565661;178565660	chr2:179430389;179430388;179430387
N2A	24256	72991;72992;72993	chr2:178565662;178565661;178565660	chr2:179430389;179430388;179430387
N2B	17759	53500;53501;53502	chr2:178565662;178565661;178565660	chr2:179430389;179430388;179430387
Novex-1	17884	53875;53876;53877	chr2:178565662;178565661;178565660	chr2:179430389;179430388;179430387
Novex-2	17951	54076;54077;54078	chr2:178565662;178565661;178565660	chr2:179430389;179430388;179430387
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-83
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.2947
• Predicted PPI site: N

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	rs1237485492	-0.458	0.001	N	0.095	0.105	0.158396225186	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
T/A	rs1237485492	-0.458	0.001	N	0.095	0.105	0.158396225186	gnomAD-4.0.0	1.59157E-06	None	None	None	None	N	None	5.65995E-05	0	None	0	0	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	0.0774	likely_benign	0.0763	benign	-0.261	Destabilizing	0.001	N	0.095	neutral	N	0.510011247	None	None	N
T/C	0.3417	ambiguous	0.3649	ambiguous	-0.247	Destabilizing	0.901	D	0.326	neutral	None	None	None	None	N
T/D	0.28	likely_benign	0.2498	benign	0.088	Stabilizing	0.561	D	0.328	neutral	None	None	None	None	N
T/E	0.2121	likely_benign	0.1843	benign	0.002	Stabilizing	0.561	D	0.322	neutral	None	None	None	None	N
T/F	0.2226	likely_benign	0.2048	benign	-0.777	Destabilizing	0.901	D	0.426	neutral	None	None	None	None	N
T/G	0.1663	likely_benign	0.1686	benign	-0.375	Destabilizing	0.209	N	0.323	neutral	None	None	None	None	N
T/H	0.2387	likely_benign	0.2289	benign	-0.688	Destabilizing	0.965	D	0.404	neutral	None	None	None	None	N
T/I	0.161	likely_benign	0.1413	benign	-0.083	Destabilizing	0.326	N	0.322	neutral	N	0.489963111	None	None	N
T/K	0.1863	likely_benign	0.159	benign	-0.368	Destabilizing	0.561	D	0.316	neutral	None	None	None	None	N
T/L	0.0879	likely_benign	0.0828	benign	-0.083	Destabilizing	0.209	N	0.35	neutral	None	None	None	None	N
T/M	0.0771	likely_benign	0.0723	benign	0.051	Stabilizing	0.901	D	0.337	neutral	None	None	None	None	N
T/N	0.0984	likely_benign	0.0942	benign	-0.119	Destabilizing	0.491	N	0.251	neutral	N	0.52001481	None	None	N
T/P	0.2919	likely_benign	0.2526	benign	-0.115	Destabilizing	0.662	D	0.359	neutral	N	0.464590701	None	None	N
T/Q	0.1821	likely_benign	0.167	benign	-0.363	Destabilizing	0.901	D	0.377	neutral	None	None	None	None	N
T/R	0.1655	likely_benign	0.1417	benign	-0.093	Destabilizing	0.561	D	0.385	neutral	None	None	None	None	N
T/S	0.0774	likely_benign	0.0798	benign	-0.302	Destabilizing	0.002	N	0.125	neutral	N	0.431296961	None	None	N
T/V	0.1178	likely_benign	0.1151	benign	-0.115	Destabilizing	0.002	N	0.109	neutral	None	None	None	None	N
T/W	0.5148	ambiguous	0.4723	ambiguous	-0.803	Destabilizing	0.991	D	0.424	neutral	None	None	None	None	N
T/Y	0.271	likely_benign	0.2583	benign	-0.515	Destabilizing	0.965	D	0.425	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.