TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16896	50911;50912;50913	chr2:178611543;178611542;178611541	chr2:179476270;179476269;179476268
N2AB	15255	45988;45989;45990	chr2:178611543;178611542;178611541	chr2:179476270;179476269;179476268
N2A	14328	43207;43208;43209	chr2:178611543;178611542;178611541	chr2:179476270;179476269;179476268
N2B	7831	23716;23717;23718	chr2:178611543;178611542;178611541	chr2:179476270;179476269;179476268
Novex-1	7956	24091;24092;24093	chr2:178611543;178611542;178611541	chr2:179476270;179476269;179476268
Novex-2	8023	24292;24293;24294	chr2:178611543;178611542;178611541	chr2:179476270;179476269;179476268
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: Fn3-11
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.4816
• 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
T/A	None	None	0.999	N	0.381	0.215	0.173771789658	gnomAD-4.0.0	2.05348E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69933E-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	0.1717	likely_benign	0.1402	benign	-0.317	Destabilizing	0.999	D	0.381	neutral	N	0.472627518	None	None	I
T/C	0.6848	likely_pathogenic	0.6473	pathogenic	-0.172	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
T/D	0.6222	likely_pathogenic	0.4963	ambiguous	0.036	Stabilizing	1.0	D	0.619	neutral	None	None	None	None	I
T/E	0.5236	ambiguous	0.3967	ambiguous	-0.032	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	I
T/F	0.6636	likely_pathogenic	0.5638	ambiguous	-0.709	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
T/G	0.353	ambiguous	0.3146	benign	-0.472	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	I
T/H	0.5609	ambiguous	0.4663	ambiguous	-0.76	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
T/I	0.6259	likely_pathogenic	0.5042	ambiguous	-0.022	Destabilizing	1.0	D	0.611	neutral	D	0.53227434	None	None	I
T/K	0.4803	ambiguous	0.3419	ambiguous	-0.469	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	I
T/L	0.2726	likely_benign	0.2218	benign	-0.022	Destabilizing	0.999	D	0.503	neutral	None	None	None	None	I
T/M	0.1896	likely_benign	0.1492	benign	0.117	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	I
T/N	0.2254	likely_benign	0.1789	benign	-0.18	Destabilizing	1.0	D	0.649	neutral	N	0.46827322	None	None	I
T/P	0.5179	ambiguous	0.3888	ambiguous	-0.091	Destabilizing	1.0	D	0.627	neutral	N	0.474783964	None	None	I
T/Q	0.4171	ambiguous	0.3206	benign	-0.398	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
T/R	0.4586	ambiguous	0.3152	benign	-0.182	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	I
T/S	0.143	likely_benign	0.1323	benign	-0.371	Destabilizing	0.999	D	0.387	neutral	N	0.442543252	None	None	I
T/V	0.4195	ambiguous	0.3548	ambiguous	-0.091	Destabilizing	0.999	D	0.458	neutral	None	None	None	None	I
T/W	0.8812	likely_pathogenic	0.8304	pathogenic	-0.736	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
T/Y	0.7222	likely_pathogenic	0.6221	pathogenic	-0.466	Destabilizing	1.0	D	0.707	prob.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.