TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24252	72979;72980;72981	chr2:178573378;178573377;178573376	chr2:179438105;179438104;179438103
N2AB	22611	68056;68057;68058	chr2:178573378;178573377;178573376	chr2:179438105;179438104;179438103
N2A	21684	65275;65276;65277	chr2:178573378;178573377;178573376	chr2:179438105;179438104;179438103
N2B	15187	45784;45785;45786	chr2:178573378;178573377;178573376	chr2:179438105;179438104;179438103
Novex-1	15312	46159;46160;46161	chr2:178573378;178573377;178573376	chr2:179438105;179438104;179438103
Novex-2	15379	46360;46361;46362	chr2:178573378;178573377;178573376	chr2:179438105;179438104;179438103
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-64
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.3523
• 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
S/T	None	None	0.999	N	0.598	0.377	0.304108284078	gnomAD-4.0.0	7.28603E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.35046E-07	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
S/A	0.1259	likely_benign	0.1296	benign	-0.528	Destabilizing	0.998	D	0.591	neutral	None	None	None	None	I
S/C	0.1004	likely_benign	0.1085	benign	-0.306	Destabilizing	1.0	D	0.761	deleterious	N	0.494262887	None	None	I
S/D	0.7591	likely_pathogenic	0.7701	pathogenic	-0.321	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	I
S/E	0.8281	likely_pathogenic	0.8369	pathogenic	-0.399	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	I
S/F	0.5082	ambiguous	0.546	ambiguous	-1.047	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
S/G	0.207	likely_benign	0.186	benign	-0.674	Destabilizing	0.999	D	0.589	neutral	N	0.489581036	None	None	I
S/H	0.5578	ambiguous	0.5894	pathogenic	-1.257	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
S/I	0.4614	ambiguous	0.5142	ambiguous	-0.264	Destabilizing	1.0	D	0.811	deleterious	N	0.507478844	None	None	I
S/K	0.8653	likely_pathogenic	0.8819	pathogenic	-0.615	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	I
S/L	0.2097	likely_benign	0.2228	benign	-0.264	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
S/M	0.341	ambiguous	0.3529	ambiguous	0.203	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
S/N	0.2168	likely_benign	0.2185	benign	-0.393	Destabilizing	0.999	D	0.741	deleterious	N	0.480980798	None	None	I
S/P	0.9752	likely_pathogenic	0.9722	pathogenic	-0.323	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
S/Q	0.7149	likely_pathogenic	0.725	pathogenic	-0.718	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
S/R	0.7865	likely_pathogenic	0.8129	pathogenic	-0.36	Destabilizing	1.0	D	0.767	deleterious	N	0.497057136	None	None	I
S/T	0.1643	likely_benign	0.1826	benign	-0.464	Destabilizing	0.999	D	0.598	neutral	N	0.499654484	None	None	I
S/V	0.3804	ambiguous	0.4254	ambiguous	-0.323	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
S/W	0.6793	likely_pathogenic	0.6891	pathogenic	-1.011	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
S/Y	0.4384	ambiguous	0.4625	ambiguous	-0.747	Destabilizing	1.0	D	0.822	deleterious	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.