TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19992	60199;60200;60201	chr2:178591845;178591844;178591843	chr2:179456572;179456571;179456570
N2AB	18351	55276;55277;55278	chr2:178591845;178591844;178591843	chr2:179456572;179456571;179456570
N2A	17424	52495;52496;52497	chr2:178591845;178591844;178591843	chr2:179456572;179456571;179456570
N2B	10927	33004;33005;33006	chr2:178591845;178591844;178591843	chr2:179456572;179456571;179456570
Novex-1	11052	33379;33380;33381	chr2:178591845;178591844;178591843	chr2:179456572;179456571;179456570
Novex-2	11119	33580;33581;33582	chr2:178591845;178591844;178591843	chr2:179456572;179456571;179456570
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: Fn3-33
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.4096
• 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	None	None	0.928	N	0.435	0.497	0.335414705075	gnomAD-4.0.0	1.59236E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4332E-05	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	0.1542	likely_benign	0.1309	benign	-0.782	Destabilizing	0.928	D	0.435	neutral	N	0.489266592	None	None	N
T/C	0.6363	likely_pathogenic	0.6227	pathogenic	-0.58	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
T/D	0.3241	likely_benign	0.2894	benign	-0.891	Destabilizing	0.968	D	0.674	neutral	None	None	None	None	N
T/E	0.329	likely_benign	0.2922	benign	-0.897	Destabilizing	0.983	D	0.694	prob.neutral	None	None	None	None	N
T/F	0.4447	ambiguous	0.4014	ambiguous	-0.907	Destabilizing	0.997	D	0.795	deleterious	None	None	None	None	N
T/G	0.3533	ambiguous	0.3142	benign	-1.029	Destabilizing	0.895	D	0.659	neutral	None	None	None	None	N
T/H	0.2952	likely_benign	0.264	benign	-1.342	Destabilizing	0.996	D	0.774	deleterious	None	None	None	None	N
T/I	0.5441	ambiguous	0.4683	ambiguous	-0.217	Destabilizing	0.989	D	0.751	deleterious	N	0.505649327	None	None	N
T/K	0.2747	likely_benign	0.2367	benign	-0.836	Destabilizing	0.968	D	0.703	prob.neutral	None	None	None	None	N
T/L	0.2007	likely_benign	0.181	benign	-0.217	Destabilizing	0.972	D	0.641	neutral	None	None	None	None	N
T/M	0.117	likely_benign	0.1047	benign	0.184	Stabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
T/N	0.0965	likely_benign	0.0893	benign	-0.846	Destabilizing	0.085	N	0.293	neutral	N	0.469479707	None	None	N
T/P	0.81	likely_pathogenic	0.7851	pathogenic	-0.374	Destabilizing	0.989	D	0.739	prob.delet.	D	0.524260561	None	None	N
T/Q	0.2693	likely_benign	0.233	benign	-1.11	Destabilizing	0.983	D	0.742	deleterious	None	None	None	None	N
T/R	0.2479	likely_benign	0.2131	benign	-0.498	Destabilizing	0.983	D	0.751	deleterious	None	None	None	None	N
T/S	0.1221	likely_benign	0.1078	benign	-1.031	Destabilizing	0.865	D	0.417	neutral	N	0.491759134	None	None	N
T/V	0.4067	ambiguous	0.3446	ambiguous	-0.374	Destabilizing	0.972	D	0.595	neutral	None	None	None	None	N
T/W	0.7065	likely_pathogenic	0.6831	pathogenic	-0.849	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
T/Y	0.3574	ambiguous	0.3333	benign	-0.601	Destabilizing	0.997	D	0.793	deleterious	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.