TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21069	63430;63431;63432	chr2:178588202;178588201;178588200	chr2:179452929;179452928;179452927
N2AB	19428	58507;58508;58509	chr2:178588202;178588201;178588200	chr2:179452929;179452928;179452927
N2A	18501	55726;55727;55728	chr2:178588202;178588201;178588200	chr2:179452929;179452928;179452927
N2B	12004	36235;36236;36237	chr2:178588202;178588201;178588200	chr2:179452929;179452928;179452927
Novex-1	12129	36610;36611;36612	chr2:178588202;178588201;178588200	chr2:179452929;179452928;179452927
Novex-2	12196	36811;36812;36813	chr2:178588202;178588201;178588200	chr2:179452929;179452928;179452927
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-41
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.3443
• 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/A	None	None	0.061	N	0.125	0.114	0.110078149338	gnomAD-4.0.0	7.00326E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.70016E-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
T/A	0.0732	likely_benign	0.0769	benign	-0.728	Destabilizing	0.061	N	0.125	neutral	N	0.433094833	None	None	N
T/C	0.3215	likely_benign	0.3241	benign	-0.434	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	N
T/D	0.4958	ambiguous	0.5131	ambiguous	-0.271	Destabilizing	0.969	D	0.555	neutral	None	None	None	None	N
T/E	0.395	ambiguous	0.4219	ambiguous	-0.264	Destabilizing	0.969	D	0.54	neutral	None	None	None	None	N
T/F	0.2922	likely_benign	0.3073	benign	-0.794	Destabilizing	0.991	D	0.581	neutral	None	None	None	None	N
T/G	0.1552	likely_benign	0.1564	benign	-0.998	Destabilizing	0.02	N	0.313	neutral	None	None	None	None	N
T/H	0.3312	likely_benign	0.336	benign	-1.318	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	N
T/I	0.1631	likely_benign	0.1618	benign	-0.099	Destabilizing	0.134	N	0.312	neutral	N	0.440503595	None	None	N
T/K	0.3177	likely_benign	0.3497	ambiguous	-0.762	Destabilizing	0.969	D	0.547	neutral	None	None	None	None	N
T/L	0.0975	likely_benign	0.1035	benign	-0.099	Destabilizing	0.759	D	0.445	neutral	None	None	None	None	N
T/M	0.1046	likely_benign	0.1068	benign	0.145	Stabilizing	0.991	D	0.568	neutral	None	None	None	None	N
T/N	0.1305	likely_benign	0.1366	benign	-0.727	Destabilizing	0.988	D	0.495	neutral	N	0.476981683	None	None	N
T/P	0.2102	likely_benign	0.2245	benign	-0.276	Destabilizing	0.988	D	0.577	neutral	N	0.461089511	None	None	N
T/Q	0.2747	likely_benign	0.2833	benign	-0.843	Destabilizing	0.997	D	0.578	neutral	None	None	None	None	N
T/R	0.2597	likely_benign	0.2933	benign	-0.565	Destabilizing	0.991	D	0.586	neutral	None	None	None	None	N
T/S	0.1009	likely_benign	0.1056	benign	-0.964	Destabilizing	0.704	D	0.415	neutral	N	0.366888483	None	None	N
T/V	0.1194	likely_benign	0.117	benign	-0.276	Destabilizing	0.759	D	0.425	neutral	None	None	None	None	N
T/W	0.6342	likely_pathogenic	0.6502	pathogenic	-0.774	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	N
T/Y	0.3161	likely_benign	0.3279	benign	-0.531	Destabilizing	0.997	D	0.585	neutral	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.