TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24188	72787;72788;72789	chr2:178573570;178573569;178573568	chr2:179438297;179438296;179438295
N2AB	22547	67864;67865;67866	chr2:178573570;178573569;178573568	chr2:179438297;179438296;179438295
N2A	21620	65083;65084;65085	chr2:178573570;178573569;178573568	chr2:179438297;179438296;179438295
N2B	15123	45592;45593;45594	chr2:178573570;178573569;178573568	chr2:179438297;179438296;179438295
Novex-1	15248	45967;45968;45969	chr2:178573570;178573569;178573568	chr2:179438297;179438296;179438295
Novex-2	15315	46168;46169;46170	chr2:178573570;178573569;178573568	chr2:179438297;179438296;179438295
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-63
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.6481
• 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
L/F	None	None	0.998	N	0.688	0.253	0.354822389136	gnomAD-4.0.0	2.97461E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.78089E-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
L/A	0.883	likely_pathogenic	0.9289	pathogenic	-1.113	Destabilizing	0.968	D	0.537	neutral	None	None	None	None	N
L/C	0.9238	likely_pathogenic	0.9586	pathogenic	-0.772	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
L/D	0.9926	likely_pathogenic	0.9965	pathogenic	-0.207	Destabilizing	0.991	D	0.71	prob.delet.	None	None	None	None	N
L/E	0.9503	likely_pathogenic	0.9769	pathogenic	-0.232	Destabilizing	0.982	D	0.644	neutral	None	None	None	None	N
L/F	0.6498	likely_pathogenic	0.786	pathogenic	-0.756	Destabilizing	0.998	D	0.688	prob.neutral	N	0.503666852	None	None	N
L/G	0.9659	likely_pathogenic	0.9815	pathogenic	-1.381	Destabilizing	0.991	D	0.706	prob.neutral	None	None	None	None	N
L/H	0.8509	likely_pathogenic	0.9364	pathogenic	-0.46	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
L/I	0.2384	likely_benign	0.3097	benign	-0.484	Destabilizing	0.984	D	0.469	neutral	None	None	None	None	N
L/K	0.8837	likely_pathogenic	0.9381	pathogenic	-0.602	Destabilizing	0.982	D	0.612	neutral	None	None	None	None	N
L/M	0.3325	likely_benign	0.4819	ambiguous	-0.492	Destabilizing	0.994	D	0.682	prob.neutral	N	0.5112089	None	None	N
L/N	0.9354	likely_pathogenic	0.9692	pathogenic	-0.42	Destabilizing	0.991	D	0.717	prob.delet.	None	None	None	None	N
L/P	0.9653	likely_pathogenic	0.9726	pathogenic	-0.66	Destabilizing	0.995	D	0.726	prob.delet.	None	None	None	None	N
L/Q	0.7166	likely_pathogenic	0.8801	pathogenic	-0.578	Destabilizing	0.682	D	0.414	neutral	None	None	None	None	N
L/R	0.7964	likely_pathogenic	0.8811	pathogenic	-0.048	Destabilizing	0.982	D	0.694	prob.neutral	None	None	None	None	N
L/S	0.9398	likely_pathogenic	0.9748	pathogenic	-1.042	Destabilizing	0.988	D	0.626	neutral	N	0.487465248	None	None	N
L/T	0.8689	likely_pathogenic	0.9401	pathogenic	-0.942	Destabilizing	0.991	D	0.643	neutral	None	None	None	None	N
L/V	0.4034	ambiguous	0.5366	ambiguous	-0.66	Destabilizing	0.958	D	0.441	neutral	N	0.470130281	None	None	N
L/W	0.8101	likely_pathogenic	0.8987	pathogenic	-0.765	Destabilizing	0.999	D	0.709	prob.delet.	N	0.510744073	None	None	N
L/Y	0.8905	likely_pathogenic	0.9484	pathogenic	-0.539	Destabilizing	0.998	D	0.715	prob.delet.	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.