TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21811	65656;65657;65658	chr2:178583751;178583750;178583749	chr2:179448478;179448477;179448476
N2AB	20170	60733;60734;60735	chr2:178583751;178583750;178583749	chr2:179448478;179448477;179448476
N2A	19243	57952;57953;57954	chr2:178583751;178583750;178583749	chr2:179448478;179448477;179448476
N2B	12746	38461;38462;38463	chr2:178583751;178583750;178583749	chr2:179448478;179448477;179448476
Novex-1	12871	38836;38837;38838	chr2:178583751;178583750;178583749	chr2:179448478;179448477;179448476
Novex-2	12938	39037;39038;39039	chr2:178583751;178583750;178583749	chr2:179448478;179448477;179448476
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-46
• Domain position: 55
• Structural Position: 73
• Q(SASA): 0.6449
• 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
P/S	rs1424664692	-0.136	0.136	N	0.2	0.13	0.213573922156	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.98E-06	0
P/S	rs1424664692	-0.136	0.136	N	0.2	0.13	0.213573922156	gnomAD-4.0.0	1.37006E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80013E-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
P/A	0.0821	likely_benign	0.0732	benign	-2.132	Highly Destabilizing	0.005	N	0.143	neutral	N	0.519980312	None	None	I
P/C	0.5152	ambiguous	0.4169	ambiguous	-1.551	Destabilizing	0.016	N	0.292	neutral	None	None	None	None	I
P/D	0.672	likely_pathogenic	0.5777	pathogenic	-2.853	Highly Destabilizing	0.842	D	0.343	neutral	None	None	None	None	I
P/E	0.5344	ambiguous	0.4565	ambiguous	-2.704	Highly Destabilizing	0.842	D	0.367	neutral	None	None	None	None	I
P/F	0.5797	likely_pathogenic	0.4549	ambiguous	-1.34	Destabilizing	0.991	D	0.346	neutral	None	None	None	None	I
P/G	0.3564	ambiguous	0.2722	benign	-2.575	Highly Destabilizing	0.525	D	0.346	neutral	None	None	None	None	I
P/H	0.3717	ambiguous	0.2768	benign	-2.293	Highly Destabilizing	0.997	D	0.306	neutral	N	0.486550205	None	None	I
P/I	0.34	likely_benign	0.2769	benign	-0.918	Destabilizing	0.949	D	0.383	neutral	None	None	None	None	I
P/K	0.6313	likely_pathogenic	0.5168	ambiguous	-1.763	Destabilizing	0.842	D	0.367	neutral	None	None	None	None	I
P/L	0.1965	likely_benign	0.1541	benign	-0.918	Destabilizing	0.801	D	0.386	neutral	N	0.510342108	None	None	I
P/M	0.3895	ambiguous	0.3132	benign	-0.865	Destabilizing	0.991	D	0.309	neutral	None	None	None	None	I
P/N	0.4514	ambiguous	0.3446	ambiguous	-1.928	Destabilizing	0.949	D	0.367	neutral	None	None	None	None	I
P/Q	0.326	likely_benign	0.2491	benign	-1.89	Destabilizing	0.974	D	0.31	neutral	None	None	None	None	I
P/R	0.4797	ambiguous	0.3776	ambiguous	-1.429	Destabilizing	0.966	D	0.359	neutral	N	0.52003624	None	None	I
P/S	0.1424	likely_benign	0.113	benign	-2.442	Highly Destabilizing	0.136	N	0.2	neutral	N	0.488638684	None	None	I
P/T	0.1393	likely_benign	0.1122	benign	-2.185	Highly Destabilizing	0.669	D	0.335	neutral	N	0.51821223	None	None	I
P/V	0.2352	likely_benign	0.2009	benign	-1.297	Destabilizing	0.728	D	0.377	neutral	None	None	None	None	I
P/W	0.756	likely_pathogenic	0.6649	pathogenic	-1.848	Destabilizing	0.998	D	0.395	neutral	None	None	None	None	I
P/Y	0.5709	likely_pathogenic	0.451	ambiguous	-1.528	Destabilizing	0.991	D	0.342	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.