TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31797	95614;95615;95616	chr2:178545847;178545846;178545845	chr2:179410574;179410573;179410572
N2AB	30156	90691;90692;90693	chr2:178545847;178545846;178545845	chr2:179410574;179410573;179410572
N2A	29229	87910;87911;87912	chr2:178545847;178545846;178545845	chr2:179410574;179410573;179410572
N2B	22732	68419;68420;68421	chr2:178545847;178545846;178545845	chr2:179410574;179410573;179410572
Novex-1	22857	68794;68795;68796	chr2:178545847;178545846;178545845	chr2:179410574;179410573;179410572
Novex-2	22924	68995;68996;68997	chr2:178545847;178545846;178545845	chr2:179410574;179410573;179410572
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: Fn3-119
• Domain position: 90
• Structural Position: 125
• Q(SASA): 0.7735
• 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
E/K	rs1381214987	None	0.1	N	0.546	0.137	0.192905019026	gnomAD-4.0.0	6.84261E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99533E-07	0	0
E/Q	rs1381214987	0.339	0.002	N	0.361	0.105	0.124217242631	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/Q	rs1381214987	0.339	0.002	N	0.361	0.105	0.124217242631	gnomAD-4.0.0	1.36852E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79907E-06	0	0
E/V	rs1183343848	0.393	0.437	N	0.586	0.157	0.482283251092	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/V	rs1183343848	0.393	0.437	N	0.586	0.157	0.482283251092	gnomAD-4.0.0	4.7745E-06	None	None	None	None	N	None	0	2.28676E-05	None	0	0	None	0	0	2.85881E-06	0	3.0248E-05

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	0.0989	likely_benign	0.099	benign	-0.091	Destabilizing	0.044	N	0.495	neutral	N	0.515545645	None	None	N
E/C	0.6319	likely_pathogenic	0.6345	pathogenic	-0.288	Destabilizing	0.96	D	0.603	neutral	None	None	None	None	N
E/D	0.0752	likely_benign	0.0728	benign	-0.307	Destabilizing	0.001	N	0.283	neutral	N	0.512486697	None	None	N
E/F	0.5487	ambiguous	0.5144	ambiguous	-0.028	Destabilizing	0.864	D	0.589	neutral	None	None	None	None	N
E/G	0.1017	likely_benign	0.0966	benign	-0.226	Destabilizing	0.001	N	0.439	neutral	N	0.492196789	None	None	N
E/H	0.3174	likely_benign	0.3074	benign	0.599	Stabilizing	0.507	D	0.507	neutral	None	None	None	None	N
E/I	0.1958	likely_benign	0.1958	benign	0.216	Stabilizing	0.676	D	0.601	neutral	None	None	None	None	N
E/K	0.1037	likely_benign	0.0935	benign	0.353	Stabilizing	0.1	N	0.546	neutral	N	0.484559785	None	None	N
E/L	0.2074	likely_benign	0.1975	benign	0.216	Stabilizing	0.507	D	0.594	neutral	None	None	None	None	N
E/M	0.2594	likely_benign	0.2588	benign	-0.029	Destabilizing	0.887	D	0.597	neutral	None	None	None	None	N
E/N	0.1377	likely_benign	0.1338	benign	0.017	Stabilizing	0.227	N	0.53	neutral	None	None	None	None	N
E/P	0.2196	likely_benign	0.2269	benign	0.132	Stabilizing	0.676	D	0.605	neutral	None	None	None	None	N
E/Q	0.103	likely_benign	0.1043	benign	0.05	Stabilizing	0.002	N	0.361	neutral	N	0.481445913	None	None	N
E/R	0.1886	likely_benign	0.1792	benign	0.65	Stabilizing	0.34	N	0.523	neutral	None	None	None	None	N
E/S	0.113	likely_benign	0.1131	benign	-0.118	Destabilizing	0.011	N	0.326	neutral	None	None	None	None	N
E/T	0.1305	likely_benign	0.1318	benign	0.005	Stabilizing	0.128	N	0.566	neutral	None	None	None	None	N
E/V	0.1285	likely_benign	0.1315	benign	0.132	Stabilizing	0.437	N	0.586	neutral	N	0.490422362	None	None	N
E/W	0.7838	likely_pathogenic	0.7641	pathogenic	0.057	Stabilizing	0.96	D	0.648	neutral	None	None	None	None	N
E/Y	0.413	ambiguous	0.3903	ambiguous	0.202	Stabilizing	0.676	D	0.616	neutral	None	None	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.