TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17355	52288;52289;52290	chr2:178609247;178609246;178609245	chr2:179473974;179473973;179473972
N2AB	15714	47365;47366;47367	chr2:178609247;178609246;178609245	chr2:179473974;179473973;179473972
N2A	14787	44584;44585;44586	chr2:178609247;178609246;178609245	chr2:179473974;179473973;179473972
N2B	8290	25093;25094;25095	chr2:178609247;178609246;178609245	chr2:179473974;179473973;179473972
Novex-1	8415	25468;25469;25470	chr2:178609247;178609246;178609245	chr2:179473974;179473973;179473972
Novex-2	8482	25669;25670;25671	chr2:178609247;178609246;178609245	chr2:179473974;179473973;179473972
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-112
• Domain position: 105
• Structural Position: 163
• Q(SASA): 1.1189
• 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
H/D	rs2055715611	None	1.0	N	0.633	0.515	0.430351802785	gnomAD-4.0.0	7.24267E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.42625E-05	0
H/N	None	None	0.999	N	0.639	0.48	0.406394481233	gnomAD-4.0.0	1.44854E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.8525E-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	0.6142	likely_pathogenic	0.5756	pathogenic	0.491	Stabilizing	0.999	D	0.596	neutral	None	None	None	None	I
H/C	0.2465	likely_benign	0.2201	benign	0.674	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
H/D	0.7141	likely_pathogenic	0.6738	pathogenic	0.003	Stabilizing	1.0	D	0.633	neutral	N	0.492440733	None	None	I
H/E	0.744	likely_pathogenic	0.6852	pathogenic	-0.007	Destabilizing	0.999	D	0.638	neutral	None	None	None	None	I
H/F	0.4556	ambiguous	0.4064	ambiguous	0.831	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	I
H/G	0.7149	likely_pathogenic	0.6717	pathogenic	0.288	Stabilizing	0.999	D	0.594	neutral	None	None	None	None	I
H/I	0.6691	likely_pathogenic	0.5927	pathogenic	0.977	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	I
H/K	0.5161	ambiguous	0.4742	ambiguous	0.459	Stabilizing	1.0	D	0.624	neutral	None	None	None	None	I
H/L	0.3288	likely_benign	0.2706	benign	0.977	Stabilizing	1.0	D	0.639	neutral	N	0.476451326	None	None	I
H/M	0.7425	likely_pathogenic	0.7	pathogenic	0.732	Stabilizing	1.0	D	0.662	neutral	None	None	None	None	I
H/N	0.3204	likely_benign	0.2841	benign	0.442	Stabilizing	0.999	D	0.639	neutral	N	0.519474171	None	None	I
H/P	0.8815	likely_pathogenic	0.8399	pathogenic	0.839	Stabilizing	1.0	D	0.653	neutral	N	0.503961622	None	None	I
H/Q	0.4982	ambiguous	0.4346	ambiguous	0.463	Stabilizing	1.0	D	0.683	prob.neutral	D	0.523514554	None	None	I
H/R	0.2397	likely_benign	0.2093	benign	0.04	Stabilizing	1.0	D	0.66	neutral	N	0.485603878	None	None	I
H/S	0.5378	ambiguous	0.5103	ambiguous	0.515	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	I
H/T	0.6478	likely_pathogenic	0.6145	pathogenic	0.595	Stabilizing	1.0	D	0.646	neutral	None	None	None	None	I
H/V	0.583	likely_pathogenic	0.5193	ambiguous	0.839	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	I
H/W	0.6314	likely_pathogenic	0.5935	pathogenic	0.681	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
H/Y	0.1915	likely_benign	0.1605	benign	1.02	Stabilizing	0.999	D	0.584	neutral	N	0.515452431	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.