TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30767	92524;92525;92526	chr2:178549327;178549326;178549325	chr2:179414054;179414053;179414052
N2AB	29126	87601;87602;87603	chr2:178549327;178549326;178549325	chr2:179414054;179414053;179414052
N2A	28199	84820;84821;84822	chr2:178549327;178549326;178549325	chr2:179414054;179414053;179414052
N2B	21702	65329;65330;65331	chr2:178549327;178549326;178549325	chr2:179414054;179414053;179414052
Novex-1	21827	65704;65705;65706	chr2:178549327;178549326;178549325	chr2:179414054;179414053;179414052
Novex-2	21894	65905;65906;65907	chr2:178549327;178549326;178549325	chr2:179414054;179414053;179414052
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-112
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.3464
• 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
V/A	rs1698403843	None	0.999	D	0.619	0.313	0.666729369348	gnomAD-4.0.0	4.77318E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57358E-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
V/A	0.4902	ambiguous	0.4402	ambiguous	-1.241	Destabilizing	0.999	D	0.619	neutral	D	0.522655257	None	None	N
V/C	0.8216	likely_pathogenic	0.797	pathogenic	-0.859	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
V/D	0.8203	likely_pathogenic	0.7768	pathogenic	-0.944	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/E	0.6417	likely_pathogenic	0.5937	pathogenic	-0.961	Destabilizing	1.0	D	0.785	deleterious	N	0.511939618	None	None	N
V/F	0.2993	likely_benign	0.2634	benign	-0.898	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
V/G	0.4433	ambiguous	0.389	ambiguous	-1.52	Destabilizing	1.0	D	0.798	deleterious	N	0.487702294	None	None	N
V/H	0.806	likely_pathogenic	0.7471	pathogenic	-0.921	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/I	0.0957	likely_benign	0.0907	benign	-0.589	Destabilizing	0.997	D	0.549	neutral	N	0.45835585	None	None	N
V/K	0.7217	likely_pathogenic	0.6614	pathogenic	-1.102	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
V/L	0.3385	likely_benign	0.3015	benign	-0.589	Destabilizing	0.997	D	0.592	neutral	N	0.497778243	None	None	N
V/M	0.2282	likely_benign	0.2117	benign	-0.505	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
V/N	0.5364	ambiguous	0.4751	ambiguous	-0.916	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
V/P	0.974	likely_pathogenic	0.9663	pathogenic	-0.771	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
V/Q	0.5168	ambiguous	0.4577	ambiguous	-1.097	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/R	0.6689	likely_pathogenic	0.6095	pathogenic	-0.526	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/S	0.5013	ambiguous	0.4459	ambiguous	-1.413	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
V/T	0.4058	ambiguous	0.3733	ambiguous	-1.327	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
V/W	0.9178	likely_pathogenic	0.8896	pathogenic	-1.048	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/Y	0.7027	likely_pathogenic	0.6463	pathogenic	-0.775	Destabilizing	1.0	D	0.785	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.