TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22561	67906;67907;67908	chr2:178579349;178579348;178579347	chr2:179444076;179444075;179444074
N2AB	20920	62983;62984;62985	chr2:178579349;178579348;178579347	chr2:179444076;179444075;179444074
N2A	19993	60202;60203;60204	chr2:178579349;178579348;178579347	chr2:179444076;179444075;179444074
N2B	13496	40711;40712;40713	chr2:178579349;178579348;178579347	chr2:179444076;179444075;179444074
Novex-1	13621	41086;41087;41088	chr2:178579349;178579348;178579347	chr2:179444076;179444075;179444074
Novex-2	13688	41287;41288;41289	chr2:178579349;178579348;178579347	chr2:179444076;179444075;179444074
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: Ig-127
• Domain position: 2
• Structural Position: 14
• Q(SASA): 0.807
• Predicted PPI site: I

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	rs876658076	None	0.966	N	0.353	0.164	0.281381271821	gnomAD-4.0.0	1.38023E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80786E-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	0.2551	likely_benign	0.2514	benign	-0.955	Destabilizing	0.525	D	0.406	neutral	None	None	None	None	I
L/C	0.5538	ambiguous	0.5607	ambiguous	-0.683	Destabilizing	0.998	D	0.321	neutral	None	None	None	None	I
L/D	0.7169	likely_pathogenic	0.7022	pathogenic	-0.34	Destabilizing	0.949	D	0.363	neutral	None	None	None	None	I
L/E	0.4092	ambiguous	0.3849	ambiguous	-0.369	Destabilizing	0.949	D	0.367	neutral	None	None	None	None	I
L/F	0.1521	likely_benign	0.1516	benign	-0.657	Destabilizing	0.966	D	0.353	neutral	N	0.446954272	None	None	I
L/G	0.6268	likely_pathogenic	0.6292	pathogenic	-1.194	Destabilizing	0.949	D	0.355	neutral	None	None	None	None	I
L/H	0.2278	likely_benign	0.2293	benign	-0.297	Destabilizing	0.998	D	0.342	neutral	None	None	None	None	I
L/I	0.0722	likely_benign	0.0731	benign	-0.405	Destabilizing	0.029	N	0.233	neutral	None	None	None	None	I
L/K	0.3548	ambiguous	0.3505	ambiguous	-0.585	Destabilizing	0.949	D	0.365	neutral	None	None	None	None	I
L/M	0.1146	likely_benign	0.1174	benign	-0.521	Destabilizing	0.966	D	0.355	neutral	N	0.458075343	None	None	I
L/N	0.3873	ambiguous	0.3863	ambiguous	-0.438	Destabilizing	0.949	D	0.359	neutral	None	None	None	None	I
L/P	0.4729	ambiguous	0.4346	ambiguous	-0.556	Destabilizing	0.974	D	0.357	neutral	None	None	None	None	I
L/Q	0.186	likely_benign	0.1852	benign	-0.589	Destabilizing	0.974	D	0.349	neutral	None	None	None	None	I
L/R	0.2569	likely_benign	0.2577	benign	-0.045	Destabilizing	0.974	D	0.358	neutral	None	None	None	None	I
L/S	0.2887	likely_benign	0.2844	benign	-0.96	Destabilizing	0.669	D	0.399	neutral	N	0.426885644	None	None	I
L/T	0.1461	likely_benign	0.143	benign	-0.872	Destabilizing	0.029	N	0.252	neutral	None	None	None	None	I
L/V	0.0688	likely_benign	0.0694	benign	-0.556	Destabilizing	0.005	N	0.199	neutral	N	0.34869422	None	None	I
L/W	0.2943	likely_benign	0.2932	benign	-0.695	Destabilizing	0.997	D	0.424	neutral	N	0.477007821	None	None	I
L/Y	0.3736	ambiguous	0.369	ambiguous	-0.464	Destabilizing	0.991	D	0.313	neutral	None	None	None	None	I

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.