TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5687	17284;17285;17286	chr2:178731816;178731815;178731814	chr2:179596543;179596542;179596541
N2AB	5370	16333;16334;16335	chr2:178731816;178731815;178731814	chr2:179596543;179596542;179596541
N2A	4443	13552;13553;13554	chr2:178731816;178731815;178731814	chr2:179596543;179596542;179596541
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-40
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.6751
• 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
I/V	None	None	None	N	0.247	0.075	0.124217242631	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
I/A	0.1787	likely_benign	0.2346	benign	-0.806	Destabilizing	0.007	N	0.378	neutral	None	None	None	None	I
I/C	0.3837	ambiguous	0.4777	ambiguous	-0.782	Destabilizing	0.628	D	0.576	neutral	None	None	None	None	I
I/D	0.4325	ambiguous	0.5436	ambiguous	0.016	Stabilizing	0.072	N	0.641	neutral	None	None	None	None	I
I/E	0.3565	ambiguous	0.4556	ambiguous	-0.023	Destabilizing	0.072	N	0.579	neutral	None	None	None	None	I
I/F	0.0819	likely_benign	0.0941	benign	-0.55	Destabilizing	None	N	0.297	neutral	N	0.404284583	None	None	I
I/G	0.3663	ambiguous	0.4645	ambiguous	-1.038	Destabilizing	0.072	N	0.581	neutral	None	None	None	None	I
I/H	0.2209	likely_benign	0.2828	benign	-0.3	Destabilizing	0.628	D	0.634	neutral	None	None	None	None	I
I/K	0.2169	likely_benign	0.2847	benign	-0.478	Destabilizing	None	N	0.439	neutral	None	None	None	None	I
I/L	0.0617	likely_benign	0.0779	benign	-0.292	Destabilizing	None	N	0.215	neutral	N	0.395934459	None	None	I
I/M	0.0772	likely_benign	0.0909	benign	-0.457	Destabilizing	0.005	N	0.295	neutral	N	0.496386668	None	None	I
I/N	0.1571	likely_benign	0.2002	benign	-0.33	Destabilizing	0.055	N	0.653	neutral	N	0.449208797	None	None	I
I/P	0.4605	ambiguous	0.6262	pathogenic	-0.429	Destabilizing	0.136	N	0.659	neutral	None	None	None	None	I
I/Q	0.2006	likely_benign	0.268	benign	-0.459	Destabilizing	0.214	N	0.661	neutral	None	None	None	None	I
I/R	0.1504	likely_benign	0.2012	benign	-0.023	Destabilizing	0.038	N	0.645	neutral	None	None	None	None	I
I/S	0.1364	likely_benign	0.156	benign	-0.887	Destabilizing	0.002	N	0.401	neutral	N	0.364707475	None	None	I
I/T	0.1228	likely_benign	0.1561	benign	-0.804	Destabilizing	0.001	N	0.321	neutral	N	0.458521713	None	None	I
I/V	0.0722	likely_benign	0.084	benign	-0.429	Destabilizing	None	N	0.247	neutral	N	0.399492052	None	None	I
I/W	0.4618	ambiguous	0.5433	ambiguous	-0.588	Destabilizing	0.864	D	0.618	neutral	None	None	None	None	I
I/Y	0.2638	likely_benign	0.3245	benign	-0.346	Destabilizing	0.038	N	0.605	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.