TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20544	61855;61856;61857	chr2:178590095;178590094;178590093	chr2:179454822;179454821;179454820
N2AB	18903	56932;56933;56934	chr2:178590095;178590094;178590093	chr2:179454822;179454821;179454820
N2A	17976	54151;54152;54153	chr2:178590095;178590094;178590093	chr2:179454822;179454821;179454820
N2B	11479	34660;34661;34662	chr2:178590095;178590094;178590093	chr2:179454822;179454821;179454820
Novex-1	11604	35035;35036;35037	chr2:178590095;178590094;178590093	chr2:179454822;179454821;179454820
Novex-2	11671	35236;35237;35238	chr2:178590095;178590094;178590093	chr2:179454822;179454821;179454820
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: Ig-121
• Domain position: 66
• Structural Position: 151
• Q(SASA): 0.4333
• 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/L	None	None	0.961	N	0.59	0.41	0.548865971634	gnomAD-4.0.0	6.84426E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99672E-07	0	0
H/R	rs876658073	-0.368	0.999	N	0.508	0.367	None	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
H/R	rs876658073	-0.368	0.999	N	0.508	0.367	None	gnomAD-4.0.0	2.7377E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59869E-06	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
H/A	0.6609	likely_pathogenic	0.6082	pathogenic	-0.171	Destabilizing	0.993	D	0.564	neutral	None	None	None	None	I
H/C	0.3751	ambiguous	0.3343	benign	0.68	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
H/D	0.705	likely_pathogenic	0.6819	pathogenic	-0.053	Destabilizing	0.999	D	0.617	neutral	N	0.45736692	None	None	I
H/E	0.7821	likely_pathogenic	0.7479	pathogenic	-0.002	Destabilizing	0.998	D	0.455	neutral	None	None	None	None	I
H/F	0.5809	likely_pathogenic	0.567	pathogenic	0.599	Stabilizing	0.171	N	0.32	neutral	None	None	None	None	I
H/G	0.6488	likely_pathogenic	0.6307	pathogenic	-0.499	Destabilizing	0.998	D	0.572	neutral	None	None	None	None	I
H/I	0.8687	likely_pathogenic	0.829	pathogenic	0.699	Stabilizing	0.996	D	0.702	prob.neutral	None	None	None	None	I
H/K	0.7357	likely_pathogenic	0.6821	pathogenic	-0.069	Destabilizing	0.999	D	0.614	neutral	None	None	None	None	I
H/L	0.5236	ambiguous	0.4804	ambiguous	0.699	Stabilizing	0.961	D	0.59	neutral	N	0.50125377	None	None	I
H/M	0.8294	likely_pathogenic	0.7883	pathogenic	0.617	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
H/N	0.2985	likely_benign	0.284	benign	0.09	Stabilizing	0.997	D	0.47	neutral	N	0.45942579	None	None	I
H/P	0.8571	likely_pathogenic	0.8409	pathogenic	0.434	Stabilizing	0.999	D	0.716	prob.delet.	N	0.49378908	None	None	I
H/Q	0.5018	ambiguous	0.4838	ambiguous	0.245	Stabilizing	0.999	D	0.529	neutral	N	0.435914212	None	None	I
H/R	0.4169	ambiguous	0.3878	ambiguous	-0.667	Destabilizing	0.999	D	0.508	neutral	N	0.445957848	None	None	I
H/S	0.4511	ambiguous	0.4263	ambiguous	0.128	Stabilizing	0.998	D	0.561	neutral	None	None	None	None	I
H/T	0.6713	likely_pathogenic	0.5952	pathogenic	0.273	Stabilizing	0.999	D	0.635	neutral	None	None	None	None	I
H/V	0.8006	likely_pathogenic	0.7397	pathogenic	0.434	Stabilizing	0.996	D	0.643	neutral	None	None	None	None	I
H/W	0.6635	likely_pathogenic	0.6543	pathogenic	0.68	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
H/Y	0.2138	likely_benign	0.2129	benign	0.94	Stabilizing	0.961	D	0.444	neutral	N	0.483188084	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.