TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22169	66730;66731;66732	chr2:178581763;178581762;178581761	chr2:179446490;179446489;179446488
N2AB	20528	61807;61808;61809	chr2:178581763;178581762;178581761	chr2:179446490;179446489;179446488
N2A	19601	59026;59027;59028	chr2:178581763;178581762;178581761	chr2:179446490;179446489;179446488
N2B	13104	39535;39536;39537	chr2:178581763;178581762;178581761	chr2:179446490;179446489;179446488
Novex-1	13229	39910;39911;39912	chr2:178581763;178581762;178581761	chr2:179446490;179446489;179446488
Novex-2	13296	40111;40112;40113	chr2:178581763;178581762;178581761	chr2:179446490;179446489;179446488
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: Fn3-49
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2213
• 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/I	None	None	1.0	N	0.785	0.458	0.543778624532	gnomAD-4.0.0	1.61167E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89256E-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	0.4626	ambiguous	0.4345	ambiguous	-0.463	Destabilizing	0.999	D	0.47	neutral	N	0.476767743	None	None	N
T/C	0.8089	likely_pathogenic	0.8249	pathogenic	-0.443	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
T/D	0.8368	likely_pathogenic	0.8489	pathogenic	-1.206	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
T/E	0.9031	likely_pathogenic	0.9037	pathogenic	-1.237	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
T/F	0.8976	likely_pathogenic	0.9168	pathogenic	-0.955	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
T/G	0.3969	ambiguous	0.4115	ambiguous	-0.644	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
T/H	0.6522	likely_pathogenic	0.6938	pathogenic	-1.142	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
T/I	0.9516	likely_pathogenic	0.9565	pathogenic	-0.086	Destabilizing	1.0	D	0.785	deleterious	N	0.503216564	None	None	N
T/K	0.721	likely_pathogenic	0.7279	pathogenic	-0.562	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
T/L	0.6622	likely_pathogenic	0.6861	pathogenic	-0.086	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
T/M	0.5662	likely_pathogenic	0.5541	ambiguous	0.409	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
T/N	0.4255	ambiguous	0.4374	ambiguous	-0.674	Destabilizing	1.0	D	0.774	deleterious	D	0.525812993	None	None	N
T/P	0.926	likely_pathogenic	0.927	pathogenic	-0.183	Destabilizing	1.0	D	0.763	deleterious	N	0.51819372	None	None	N
T/Q	0.7093	likely_pathogenic	0.7154	pathogenic	-1.036	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
T/R	0.6975	likely_pathogenic	0.6958	pathogenic	-0.221	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
T/S	0.1757	likely_benign	0.1682	benign	-0.714	Destabilizing	0.999	D	0.501	neutral	N	0.427168938	None	None	N
T/V	0.8335	likely_pathogenic	0.8462	pathogenic	-0.183	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
T/W	0.9735	likely_pathogenic	0.9788	pathogenic	-0.974	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
T/Y	0.868	likely_pathogenic	0.9007	pathogenic	-0.628	Destabilizing	1.0	D	0.778	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.