TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30060	90403;90404;90405	chr2:178552722;178552721;178552720	chr2:179417449;179417448;179417447
N2AB	28419	85480;85481;85482	chr2:178552722;178552721;178552720	chr2:179417449;179417448;179417447
N2A	27492	82699;82700;82701	chr2:178552722;178552721;178552720	chr2:179417449;179417448;179417447
N2B	20995	63208;63209;63210	chr2:178552722;178552721;178552720	chr2:179417449;179417448;179417447
Novex-1	21120	63583;63584;63585	chr2:178552722;178552721;178552720	chr2:179417449;179417448;179417447
Novex-2	21187	63784;63785;63786	chr2:178552722;178552721;178552720	chr2:179417449;179417448;179417447
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-107
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.1644
• 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
S/C	None	None	1.0	N	0.835	0.537	0.413761986042	gnomAD-4.0.0	1.59102E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02389E-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
S/A	0.228	likely_benign	0.1831	benign	-0.594	Destabilizing	0.998	D	0.619	neutral	None	None	None	None	N
S/C	0.253	likely_benign	0.2316	benign	-0.451	Destabilizing	1.0	D	0.835	deleterious	N	0.491300373	None	None	N
S/D	0.9019	likely_pathogenic	0.8844	pathogenic	-0.448	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
S/E	0.9505	likely_pathogenic	0.9398	pathogenic	-0.492	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
S/F	0.7713	likely_pathogenic	0.69	pathogenic	-0.932	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
S/G	0.3481	ambiguous	0.3027	benign	-0.791	Destabilizing	0.999	D	0.613	neutral	N	0.48414976	None	None	N
S/H	0.865	likely_pathogenic	0.8431	pathogenic	-1.333	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
S/I	0.813	likely_pathogenic	0.7181	pathogenic	-0.19	Destabilizing	1.0	D	0.837	deleterious	N	0.498262132	None	None	N
S/K	0.9884	likely_pathogenic	0.9847	pathogenic	-0.761	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
S/L	0.4471	ambiguous	0.3443	ambiguous	-0.19	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
S/M	0.5853	likely_pathogenic	0.4972	ambiguous	0.213	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
S/N	0.6073	likely_pathogenic	0.568	pathogenic	-0.629	Destabilizing	0.999	D	0.729	prob.delet.	N	0.501553815	None	None	N
S/P	0.9923	likely_pathogenic	0.9874	pathogenic	-0.293	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
S/Q	0.9332	likely_pathogenic	0.9206	pathogenic	-0.898	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
S/R	0.9783	likely_pathogenic	0.9728	pathogenic	-0.544	Destabilizing	1.0	D	0.84	deleterious	N	0.496234216	None	None	N
S/T	0.2308	likely_benign	0.1755	benign	-0.66	Destabilizing	0.999	D	0.631	neutral	N	0.486487753	None	None	N
S/V	0.709	likely_pathogenic	0.6069	pathogenic	-0.293	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
S/W	0.8746	likely_pathogenic	0.8298	pathogenic	-0.895	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
S/Y	0.7414	likely_pathogenic	0.6853	pathogenic	-0.639	Destabilizing	1.0	D	0.85	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.