TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14305	43138;43139;43140	chr2:178633446;178633445;178633444	chr2:179498173;179498172;179498171
N2AB	12664	38215;38216;38217	chr2:178633446;178633445;178633444	chr2:179498173;179498172;179498171
N2A	11737	35434;35435;35436	chr2:178633446;178633445;178633444	chr2:179498173;179498172;179498171
N2B	5240	15943;15944;15945	chr2:178633446;178633445;178633444	chr2:179498173;179498172;179498171
Novex-1	5365	16318;16319;16320	chr2:178633446;178633445;178633444	chr2:179498173;179498172;179498171
Novex-2	5432	16519;16520;16521	chr2:178633446;178633445;178633444	chr2:179498173;179498172;179498171
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: Ig-93
• Domain position: 75
• Structural Position: 161
• Q(SASA): 1.011
• 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	D	0.735	0.475	0.640098834198	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.1448	likely_benign	0.1145	benign	-0.276	Destabilizing	0.999	D	0.555	neutral	N	0.503359503	None	None	N
T/C	0.7584	likely_pathogenic	0.6491	pathogenic	-0.196	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
T/D	0.4841	ambiguous	0.4013	ambiguous	0.064	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
T/E	0.4187	ambiguous	0.3307	benign	-0.016	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
T/F	0.4431	ambiguous	0.3304	benign	-0.783	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
T/G	0.3641	ambiguous	0.2942	benign	-0.399	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
T/H	0.4346	ambiguous	0.3476	ambiguous	-0.661	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
T/I	0.3635	ambiguous	0.2337	benign	-0.071	Destabilizing	1.0	D	0.735	prob.delet.	D	0.607530484	None	None	N
T/K	0.2771	likely_benign	0.2142	benign	-0.347	Destabilizing	1.0	D	0.738	prob.delet.	N	0.508759757	None	None	N
T/L	0.2111	likely_benign	0.1532	benign	-0.071	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	N
T/M	0.1448	likely_benign	0.1173	benign	0.069	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
T/N	0.1689	likely_benign	0.1333	benign	-0.098	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
T/P	0.2529	likely_benign	0.2404	benign	-0.111	Destabilizing	1.0	D	0.726	prob.delet.	D	0.547728382	None	None	N
T/Q	0.3486	ambiguous	0.2823	benign	-0.334	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
T/R	0.2466	likely_benign	0.2043	benign	-0.043	Destabilizing	1.0	D	0.731	prob.delet.	N	0.510757044	None	None	N
T/S	0.1557	likely_benign	0.1342	benign	-0.286	Destabilizing	0.999	D	0.585	neutral	N	0.485117775	None	None	N
T/V	0.3154	likely_benign	0.2158	benign	-0.111	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
T/W	0.7896	likely_pathogenic	0.7361	pathogenic	-0.814	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
T/Y	0.5178	ambiguous	0.4037	ambiguous	-0.523	Destabilizing	1.0	D	0.725	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.