TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29686	89281;89282;89283	chr2:178554055;178554054;178554053	chr2:179418782;179418781;179418780
N2AB	28045	84358;84359;84360	chr2:178554055;178554054;178554053	chr2:179418782;179418781;179418780
N2A	27118	81577;81578;81579	chr2:178554055;178554054;178554053	chr2:179418782;179418781;179418780
N2B	20621	62086;62087;62088	chr2:178554055;178554054;178554053	chr2:179418782;179418781;179418780
Novex-1	20746	62461;62462;62463	chr2:178554055;178554054;178554053	chr2:179418782;179418781;179418780
Novex-2	20813	62662;62663;62664	chr2:178554055;178554054;178554053	chr2:179418782;179418781;179418780
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-104
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.6762
• 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
E/D	rs1164496806	-0.22	0.035	N	0.141	0.071	0.202086224978	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/K	None	None	0.92	N	0.435	0.256	0.271763555656	gnomAD-4.0.0	6.84199E-07	None	None	None	None	I	None	0	0	None	0	2.51915E-05	None	0	0	0	0	0
E/Q	None	None	0.959	N	0.435	0.243	0.267755039894	gnomAD-4.0.0	6.84199E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99444E-07	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
E/A	0.2619	likely_benign	0.2929	benign	-0.029	Destabilizing	0.826	D	0.459	neutral	N	0.438305865	None	None	I
E/C	0.8983	likely_pathogenic	0.9139	pathogenic	-0.348	Destabilizing	0.999	D	0.517	neutral	None	None	None	None	I
E/D	0.0758	likely_benign	0.0805	benign	-0.325	Destabilizing	0.035	N	0.141	neutral	N	0.4190481	None	None	I
E/F	0.8698	likely_pathogenic	0.8965	pathogenic	0.04	Stabilizing	0.997	D	0.437	neutral	None	None	None	None	I
E/G	0.1869	likely_benign	0.2061	benign	-0.158	Destabilizing	0.015	N	0.206	neutral	N	0.456643696	None	None	I
E/H	0.6524	likely_pathogenic	0.7009	pathogenic	0.713	Stabilizing	0.997	D	0.431	neutral	None	None	None	None	I
E/I	0.603	likely_pathogenic	0.6454	pathogenic	0.258	Stabilizing	0.997	D	0.439	neutral	None	None	None	None	I
E/K	0.3741	ambiguous	0.404	ambiguous	0.369	Stabilizing	0.92	D	0.435	neutral	N	0.433401477	None	None	I
E/L	0.6625	likely_pathogenic	0.7017	pathogenic	0.258	Stabilizing	0.991	D	0.416	neutral	None	None	None	None	I
E/M	0.6661	likely_pathogenic	0.7094	pathogenic	-0.059	Destabilizing	0.999	D	0.442	neutral	None	None	None	None	I
E/N	0.2512	likely_benign	0.2656	benign	-0.01	Destabilizing	0.939	D	0.442	neutral	None	None	None	None	I
E/P	0.8157	likely_pathogenic	0.861	pathogenic	0.18	Stabilizing	0.997	D	0.443	neutral	None	None	None	None	I
E/Q	0.2769	likely_benign	0.2931	benign	0.028	Stabilizing	0.959	D	0.435	neutral	N	0.46984228	None	None	I
E/R	0.5497	ambiguous	0.6002	pathogenic	0.674	Stabilizing	0.991	D	0.439	neutral	None	None	None	None	I
E/S	0.2709	likely_benign	0.2897	benign	-0.127	Destabilizing	0.939	D	0.429	neutral	None	None	None	None	I
E/T	0.3011	likely_benign	0.3193	benign	-0.007	Destabilizing	0.969	D	0.449	neutral	None	None	None	None	I
E/V	0.3619	ambiguous	0.4015	ambiguous	0.18	Stabilizing	0.996	D	0.427	neutral	N	0.450288153	None	None	I
E/W	0.9497	likely_pathogenic	0.9637	pathogenic	0.114	Stabilizing	0.999	D	0.597	neutral	None	None	None	None	I
E/Y	0.7124	likely_pathogenic	0.7631	pathogenic	0.267	Stabilizing	0.997	D	0.445	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.