TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21616	65071;65072;65073	chr2:178584795;178584794;178584793	chr2:179449522;179449521;179449520
N2AB	19975	60148;60149;60150	chr2:178584795;178584794;178584793	chr2:179449522;179449521;179449520
N2A	19048	57367;57368;57369	chr2:178584795;178584794;178584793	chr2:179449522;179449521;179449520
N2B	12551	37876;37877;37878	chr2:178584795;178584794;178584793	chr2:179449522;179449521;179449520
Novex-1	12676	38251;38252;38253	chr2:178584795;178584794;178584793	chr2:179449522;179449521;179449520
Novex-2	12743	38452;38453;38454	chr2:178584795;178584794;178584793	chr2:179449522;179449521;179449520
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-44
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.3946
• 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
K/E	rs761445537	0.39	0.999	N	0.557	0.391	0.268660756437	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	4.64E-05	8.91E-06	0
K/E	rs761445537	0.39	0.999	N	0.557	0.391	0.268660756437	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs761445537	0.39	0.999	N	0.557	0.391	0.268660756437	gnomAD-4.0.0	8.97105E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.56858E-05	0	1.19715E-05	0	2.8456E-05

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
K/A	0.7391	likely_pathogenic	0.7095	pathogenic	0.039	Stabilizing	0.999	D	0.629	neutral	None	None	None	None	I
K/C	0.9025	likely_pathogenic	0.8893	pathogenic	-0.356	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
K/D	0.8958	likely_pathogenic	0.8707	pathogenic	0.048	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	I
K/E	0.674	likely_pathogenic	0.6158	pathogenic	0.065	Stabilizing	0.999	D	0.557	neutral	N	0.457832988	None	None	I
K/F	0.9754	likely_pathogenic	0.9679	pathogenic	-0.176	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
K/G	0.718	likely_pathogenic	0.6744	pathogenic	-0.149	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	I
K/H	0.5965	likely_pathogenic	0.5625	ambiguous	-0.293	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	I
K/I	0.8911	likely_pathogenic	0.8752	pathogenic	0.454	Stabilizing	1.0	D	0.668	neutral	D	0.523695407	None	None	I
K/L	0.8233	likely_pathogenic	0.8073	pathogenic	0.454	Stabilizing	1.0	D	0.597	neutral	None	None	None	None	I
K/M	0.7448	likely_pathogenic	0.7164	pathogenic	0.07	Stabilizing	1.0	D	0.616	neutral	None	None	None	None	I
K/N	0.8263	likely_pathogenic	0.7916	pathogenic	0.088	Stabilizing	1.0	D	0.663	neutral	N	0.496759522	None	None	I
K/P	0.9577	likely_pathogenic	0.95	pathogenic	0.342	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	I
K/Q	0.3529	ambiguous	0.3306	benign	-0.021	Destabilizing	1.0	D	0.649	neutral	N	0.481982071	None	None	I
K/R	0.0866	likely_benign	0.0851	benign	-0.037	Destabilizing	0.999	D	0.509	neutral	N	0.407985744	None	None	I
K/S	0.7743	likely_pathogenic	0.7501	pathogenic	-0.361	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	I
K/T	0.584	likely_pathogenic	0.5503	ambiguous	-0.197	Destabilizing	1.0	D	0.633	neutral	N	0.473301086	None	None	I
K/V	0.8018	likely_pathogenic	0.788	pathogenic	0.342	Stabilizing	1.0	D	0.626	neutral	None	None	None	None	I
K/W	0.9582	likely_pathogenic	0.9507	pathogenic	-0.241	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
K/Y	0.9212	likely_pathogenic	0.9021	pathogenic	0.123	Stabilizing	1.0	D	0.63	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.