TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5088	15487;15488;15489	chr2:178734562;178734561;178734560	chr2:179599289;179599288;179599287
N2AB	4771	14536;14537;14538	chr2:178734562;178734561;178734560	chr2:179599289;179599288;179599287
N2A	3844	11755;11756;11757	chr2:178734562;178734561;178734560	chr2:179599289;179599288;179599287
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-34
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.5734
• 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
R/K	rs766300782	-0.104	0.002	N	0.169	0.117	0.230578612272	gnomAD-2.1.1	4.25E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.73E-05	None	0	0	0
R/K	rs766300782	-0.104	0.002	N	0.169	0.117	0.230578612272	gnomAD-4.0.0	3.27612E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	3.00716E-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
R/A	0.7966	likely_pathogenic	0.6685	pathogenic	0.006	Stabilizing	0.688	D	0.434	neutral	None	None	None	None	I
R/C	0.5993	likely_pathogenic	0.4609	ambiguous	-0.206	Destabilizing	0.998	D	0.437	neutral	None	None	None	None	I
R/D	0.9536	likely_pathogenic	0.9111	pathogenic	-0.258	Destabilizing	0.842	D	0.425	neutral	None	None	None	None	I
R/E	0.76	likely_pathogenic	0.6329	pathogenic	-0.225	Destabilizing	0.525	D	0.44	neutral	None	None	None	None	I
R/F	0.893	likely_pathogenic	0.8334	pathogenic	-0.318	Destabilizing	0.991	D	0.403	neutral	None	None	None	None	I
R/G	0.7109	likely_pathogenic	0.5559	ambiguous	-0.124	Destabilizing	0.801	D	0.466	neutral	D	0.532257251	None	None	I
R/H	0.3102	likely_benign	0.2363	benign	-0.588	Destabilizing	0.991	D	0.347	neutral	None	None	None	None	I
R/I	0.7283	likely_pathogenic	0.5833	pathogenic	0.303	Stabilizing	0.966	D	0.411	neutral	N	0.477694258	None	None	I
R/K	0.1417	likely_benign	0.1239	benign	-0.138	Destabilizing	0.002	N	0.169	neutral	N	0.385173511	None	None	I
R/L	0.6306	likely_pathogenic	0.5222	ambiguous	0.303	Stabilizing	0.842	D	0.466	neutral	None	None	None	None	I
R/M	0.7168	likely_pathogenic	0.5736	pathogenic	-0.063	Destabilizing	0.991	D	0.357	neutral	None	None	None	None	I
R/N	0.9266	likely_pathogenic	0.8705	pathogenic	0.009	Stabilizing	0.842	D	0.433	neutral	None	None	None	None	I
R/P	0.8192	likely_pathogenic	0.6957	pathogenic	0.221	Stabilizing	0.974	D	0.413	neutral	None	None	None	None	I
R/Q	0.2707	likely_benign	0.197	benign	-0.06	Destabilizing	0.842	D	0.47	neutral	None	None	None	None	I
R/S	0.892	likely_pathogenic	0.8035	pathogenic	-0.2	Destabilizing	0.801	D	0.462	neutral	N	0.49273017	None	None	I
R/T	0.7751	likely_pathogenic	0.6158	pathogenic	-0.067	Destabilizing	0.801	D	0.46	neutral	N	0.484652802	None	None	I
R/V	0.7821	likely_pathogenic	0.6628	pathogenic	0.221	Stabilizing	0.974	D	0.407	neutral	None	None	None	None	I
R/W	0.4665	ambiguous	0.3694	ambiguous	-0.485	Destabilizing	0.998	D	0.514	neutral	None	None	None	None	I
R/Y	0.7792	likely_pathogenic	0.7015	pathogenic	-0.085	Destabilizing	0.991	D	0.407	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.