TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21284	64075;64076;64077	chr2:178587361;178587360;178587359	chr2:179452088;179452087;179452086
N2AB	19643	59152;59153;59154	chr2:178587361;178587360;178587359	chr2:179452088;179452087;179452086
N2A	18716	56371;56372;56373	chr2:178587361;178587360;178587359	chr2:179452088;179452087;179452086
N2B	12219	36880;36881;36882	chr2:178587361;178587360;178587359	chr2:179452088;179452087;179452086
Novex-1	12344	37255;37256;37257	chr2:178587361;178587360;178587359	chr2:179452088;179452087;179452086
Novex-2	12411	37456;37457;37458	chr2:178587361;178587360;178587359	chr2:179452088;179452087;179452086
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-42
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.2384
• 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
H/R	rs769740117	-0.96	0.669	N	0.425	0.279	0.273503213844	gnomAD-2.1.1	1.63E-05	None	None	None	None	N	None	0	0	None	1.0008E-04	0	None	0	None	0	2.7E-05	0
H/R	rs769740117	-0.96	0.669	N	0.425	0.279	0.273503213844	gnomAD-4.0.0	6.43781E-06	None	None	None	None	N	None	0	0	None	4.33313E-05	0	None	0	0	7.46118E-06	0	0
H/Y	None	None	0.961	N	0.437	0.3	0.326074293725	gnomAD-4.0.0	1.5952E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4353E-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
H/A	0.1853	likely_benign	0.2272	benign	-0.715	Destabilizing	0.688	D	0.479	neutral	None	None	None	None	N
H/C	0.1371	likely_benign	0.1503	benign	-0.093	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
H/D	0.2385	likely_benign	0.2757	benign	-0.481	Destabilizing	0.801	D	0.481	neutral	N	0.443733114	None	None	N
H/E	0.2367	likely_benign	0.2786	benign	-0.419	Destabilizing	0.525	D	0.345	neutral	None	None	None	None	N
H/F	0.1848	likely_benign	0.1957	benign	-0.064	Destabilizing	0.991	D	0.54	neutral	None	None	None	None	N
H/G	0.2812	likely_benign	0.3307	benign	-1.032	Destabilizing	0.842	D	0.528	neutral	None	None	None	None	N
H/I	0.1679	likely_benign	0.2004	benign	0.138	Stabilizing	0.974	D	0.619	neutral	None	None	None	None	N
H/K	0.1885	likely_benign	0.209	benign	-0.624	Destabilizing	0.525	D	0.47	neutral	None	None	None	None	N
H/L	0.0805	likely_benign	0.0937	benign	0.138	Stabilizing	0.801	D	0.521	neutral	N	0.411716696	None	None	N
H/M	0.2589	likely_benign	0.3017	benign	0.082	Stabilizing	0.974	D	0.603	neutral	None	None	None	None	N
H/N	0.0987	likely_benign	0.1144	benign	-0.508	Destabilizing	0.801	D	0.457	neutral	N	0.384935526	None	None	N
H/P	0.583	likely_pathogenic	0.6445	pathogenic	-0.124	Destabilizing	0.966	D	0.579	neutral	N	0.492295065	None	None	N
H/Q	0.119	likely_benign	0.1355	benign	-0.358	Destabilizing	0.007	N	0.223	neutral	N	0.370870151	None	None	N
H/R	0.0919	likely_benign	0.0973	benign	-0.882	Destabilizing	0.669	D	0.425	neutral	N	0.414044925	None	None	N
H/S	0.1556	likely_benign	0.1851	benign	-0.617	Destabilizing	0.842	D	0.487	neutral	None	None	None	None	N
H/T	0.1477	likely_benign	0.1793	benign	-0.463	Destabilizing	0.842	D	0.507	neutral	None	None	None	None	N
H/V	0.1407	likely_benign	0.1669	benign	-0.124	Destabilizing	0.915	D	0.537	neutral	None	None	None	None	N
H/W	0.3167	likely_benign	0.3149	benign	0.057	Stabilizing	0.998	D	0.62	neutral	None	None	None	None	N
H/Y	0.0922	likely_benign	0.0916	benign	0.364	Stabilizing	0.961	D	0.437	neutral	N	0.437980578	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.