TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9903	29932;29933;29934	chr2:178704765;178704764;178704763	chr2:179569492;179569491;179569490
N2AB	9586	28981;28982;28983	chr2:178704765;178704764;178704763	chr2:179569492;179569491;179569490
N2A	8659	26200;26201;26202	chr2:178704765;178704764;178704763	chr2:179569492;179569491;179569490
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: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-84
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4073
• 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/M	rs1437200210	None	0.934	None	0.439	0.152	0.424430313326	gnomAD-4.0.0	2.05823E-06	None	None	None	None	I	None	6.00348E-05	2.24669E-05	None	0	0	None	0	0	0	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
I/A	0.8593	likely_pathogenic	0.7887	pathogenic	-0.918	Destabilizing	0.029	N	0.195	neutral	None	None	None	None	I
I/C	0.9501	likely_pathogenic	0.9199	pathogenic	-0.652	Destabilizing	0.998	D	0.398	neutral	None	None	None	None	I
I/D	0.978	likely_pathogenic	0.9518	pathogenic	-0.454	Destabilizing	0.974	D	0.436	neutral	None	None	None	None	I
I/E	0.8678	likely_pathogenic	0.784	pathogenic	-0.527	Destabilizing	0.974	D	0.401	neutral	None	None	None	None	I
I/F	0.57	likely_pathogenic	0.4414	ambiguous	-0.754	Destabilizing	0.934	D	0.398	neutral	None	None	None	None	I
I/G	0.9681	likely_pathogenic	0.9364	pathogenic	-1.128	Destabilizing	0.728	D	0.388	neutral	None	None	None	None	I
I/H	0.8782	likely_pathogenic	0.8077	pathogenic	-0.315	Destabilizing	0.998	D	0.409	neutral	None	None	None	None	I
I/K	0.7214	likely_pathogenic	0.5835	pathogenic	-0.602	Destabilizing	0.949	D	0.399	neutral	None	None	None	None	I
I/L	0.2117	likely_benign	0.1875	benign	-0.468	Destabilizing	0.005	N	0.142	neutral	None	None	None	None	I
I/M	0.2424	likely_benign	0.2042	benign	-0.42	Destabilizing	0.934	D	0.439	neutral	None	None	None	None	I
I/N	0.7597	likely_pathogenic	0.6342	pathogenic	-0.401	Destabilizing	0.989	D	0.433	neutral	None	None	None	None	I
I/P	0.9924	likely_pathogenic	0.9762	pathogenic	-0.585	Destabilizing	0.974	D	0.429	neutral	None	None	None	None	I
I/Q	0.7598	likely_pathogenic	0.6517	pathogenic	-0.634	Destabilizing	0.991	D	0.429	neutral	None	None	None	None	I
I/R	0.6772	likely_pathogenic	0.5099	ambiguous	0.031	Stabilizing	0.974	D	0.436	neutral	None	None	None	None	I
I/S	0.8319	likely_pathogenic	0.7268	pathogenic	-0.882	Destabilizing	0.669	D	0.355	neutral	None	None	None	None	I
I/T	0.6845	likely_pathogenic	0.5847	pathogenic	-0.846	Destabilizing	0.801	D	0.371	neutral	None	None	None	None	I
I/V	0.1561	likely_benign	0.1487	benign	-0.585	Destabilizing	0.005	N	0.167	neutral	None	None	None	None	I
I/W	0.9635	likely_pathogenic	0.9263	pathogenic	-0.772	Destabilizing	0.998	D	0.45	neutral	None	None	None	None	I
I/Y	0.8861	likely_pathogenic	0.8224	pathogenic	-0.544	Destabilizing	0.991	D	0.412	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.