TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21323	64192;64193;64194	chr2:178587244;178587243;178587242	chr2:179451971;179451970;179451969
N2AB	19682	59269;59270;59271	chr2:178587244;178587243;178587242	chr2:179451971;179451970;179451969
N2A	18755	56488;56489;56490	chr2:178587244;178587243;178587242	chr2:179451971;179451970;179451969
N2B	12258	36997;36998;36999	chr2:178587244;178587243;178587242	chr2:179451971;179451970;179451969
Novex-1	12383	37372;37373;37374	chr2:178587244;178587243;178587242	chr2:179451971;179451970;179451969
Novex-2	12450	37573;37574;37575	chr2:178587244;178587243;178587242	chr2:179451971;179451970;179451969
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-42
• Domain position: 58
• Structural Position: 89
• Q(SASA): 0.347
• 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	0.987	N	0.631	0.324	0.365892764245	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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	0.098	likely_benign	0.1052	benign	-0.877	Destabilizing	0.977	D	0.439	neutral	N	0.492221744	None	None	N
T/C	0.3356	likely_benign	0.3561	ambiguous	-0.427	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
T/D	0.5723	likely_pathogenic	0.5725	pathogenic	-0.104	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
T/E	0.4579	ambiguous	0.4904	ambiguous	0.024	Stabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
T/F	0.347	ambiguous	0.3886	ambiguous	-0.918	Destabilizing	0.995	D	0.715	prob.delet.	None	None	None	None	N
T/G	0.2376	likely_benign	0.2453	benign	-1.215	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	N
T/H	0.3517	ambiguous	0.3417	ambiguous	-1.258	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
T/I	0.2003	likely_benign	0.2443	benign	-0.026	Destabilizing	0.987	D	0.631	neutral	N	0.486372394	None	None	N
T/K	0.3479	ambiguous	0.316	benign	-0.09	Destabilizing	0.997	D	0.681	prob.neutral	N	0.482675865	None	None	N
T/L	0.0748	likely_benign	0.078	benign	-0.026	Destabilizing	0.15	N	0.369	neutral	None	None	None	None	N
T/M	0.0718	likely_benign	0.0776	benign	-0.08	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
T/N	0.0962	likely_benign	0.0969	benign	-0.537	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
T/P	0.1048	likely_benign	0.1004	benign	-0.278	Destabilizing	0.999	D	0.724	prob.delet.	N	0.47361051	None	None	N
T/Q	0.2725	likely_benign	0.2635	benign	-0.405	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
T/R	0.3233	likely_benign	0.2867	benign	-0.167	Destabilizing	0.997	D	0.725	prob.delet.	N	0.472596552	None	None	N
T/S	0.1267	likely_benign	0.1338	benign	-0.892	Destabilizing	0.989	D	0.404	neutral	N	0.48487791	None	None	N
T/V	0.1505	likely_benign	0.179	benign	-0.278	Destabilizing	0.966	D	0.429	neutral	None	None	None	None	N
T/W	0.7485	likely_pathogenic	0.7581	pathogenic	-0.964	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
T/Y	0.3454	ambiguous	0.3606	ambiguous	-0.589	Destabilizing	0.998	D	0.723	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.