TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18591	55996;55997;55998	chr2:178601133;178601132;178601131	chr2:179465860;179465859;179465858
N2AB	16950	51073;51074;51075	chr2:178601133;178601132;178601131	chr2:179465860;179465859;179465858
N2A	16023	48292;48293;48294	chr2:178601133;178601132;178601131	chr2:179465860;179465859;179465858
N2B	9526	28801;28802;28803	chr2:178601133;178601132;178601131	chr2:179465860;179465859;179465858
Novex-1	9651	29176;29177;29178	chr2:178601133;178601132;178601131	chr2:179465860;179465859;179465858
Novex-2	9718	29377;29378;29379	chr2:178601133;178601132;178601131	chr2:179465860;179465859;179465858
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-23
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.141
• 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
I/V	rs890362775	-1.318	None	N	0.083	0.08	None	gnomAD-2.1.1	9.81E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.07E-05	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
I/A	0.4991	ambiguous	0.475	ambiguous	-2.231	Highly Destabilizing	0.035	N	0.343	neutral	None	None	None	None	N
I/C	0.7369	likely_pathogenic	0.738	pathogenic	-1.91	Destabilizing	0.824	D	0.372	neutral	None	None	None	None	N
I/D	0.9309	likely_pathogenic	0.915	pathogenic	-2.13	Highly Destabilizing	0.555	D	0.449	neutral	None	None	None	None	N
I/E	0.7941	likely_pathogenic	0.7908	pathogenic	-2.021	Highly Destabilizing	0.555	D	0.439	neutral	None	None	None	None	N
I/F	0.3876	ambiguous	0.3566	ambiguous	-1.471	Destabilizing	0.317	N	0.423	neutral	N	0.496223592	None	None	N
I/G	0.8332	likely_pathogenic	0.8064	pathogenic	-2.648	Highly Destabilizing	0.262	N	0.406	neutral	None	None	None	None	N
I/H	0.7619	likely_pathogenic	0.7605	pathogenic	-1.875	Destabilizing	0.935	D	0.461	neutral	None	None	None	None	N
I/K	0.5444	ambiguous	0.5767	pathogenic	-1.584	Destabilizing	0.555	D	0.437	neutral	None	None	None	None	N
I/L	0.187	likely_benign	0.1731	benign	-1.09	Destabilizing	0.005	N	0.259	neutral	N	0.476538966	None	None	N
I/M	0.1754	likely_benign	0.1708	benign	-1.205	Destabilizing	0.317	N	0.462	neutral	N	0.509979536	None	None	N
I/N	0.5429	ambiguous	0.5528	ambiguous	-1.667	Destabilizing	0.741	D	0.489	neutral	D	0.523196762	None	None	N
I/P	0.829	likely_pathogenic	0.8091	pathogenic	-1.445	Destabilizing	0.791	D	0.467	neutral	None	None	None	None	N
I/Q	0.6185	likely_pathogenic	0.6306	pathogenic	-1.743	Destabilizing	0.791	D	0.496	neutral	None	None	None	None	N
I/R	0.4751	ambiguous	0.5023	ambiguous	-1.128	Destabilizing	0.555	D	0.488	neutral	None	None	None	None	N
I/S	0.5088	ambiguous	0.4974	ambiguous	-2.38	Highly Destabilizing	0.117	N	0.367	neutral	N	0.498858465	None	None	N
I/T	0.2703	likely_benign	0.2698	benign	-2.142	Highly Destabilizing	0.062	N	0.37	neutral	N	0.481195424	None	None	N
I/V	0.0658	likely_benign	0.063	benign	-1.445	Destabilizing	None	N	0.083	neutral	N	0.368080562	None	None	N
I/W	0.9377	likely_pathogenic	0.9242	pathogenic	-1.62	Destabilizing	0.935	D	0.516	neutral	None	None	None	None	N
I/Y	0.7476	likely_pathogenic	0.7486	pathogenic	-1.368	Destabilizing	0.555	D	0.381	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.