TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16366	49321;49322;49323	chr2:178614301;178614300;178614299	chr2:179479028;179479027;179479026
N2AB	14725	44398;44399;44400	chr2:178614301;178614300;178614299	chr2:179479028;179479027;179479026
N2A	13798	41617;41618;41619	chr2:178614301;178614300;178614299	chr2:179479028;179479027;179479026
N2B	7301	22126;22127;22128	chr2:178614301;178614300;178614299	chr2:179479028;179479027;179479026
Novex-1	7426	22501;22502;22503	chr2:178614301;178614300;178614299	chr2:179479028;179479027;179479026
Novex-2	7493	22702;22703;22704	chr2:178614301;178614300;178614299	chr2:179479028;179479027;179479026
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: Fn3-6
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.5805
• 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/A	None	None	0.885	N	0.479	0.264	0.35139820857	gnomAD-4.0.0	5.47649E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49894E-06	0	4.97413E-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	0.3843	ambiguous	0.3292	benign	-0.761	Destabilizing	0.885	D	0.479	neutral	N	0.468932288	None	None	N
E/C	0.9455	likely_pathogenic	0.9236	pathogenic	-0.182	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
E/D	0.1544	likely_benign	0.1306	benign	-0.794	Destabilizing	0.046	N	0.239	neutral	N	0.42543548	None	None	N
E/F	0.9231	likely_pathogenic	0.901	pathogenic	-0.633	Destabilizing	0.986	D	0.632	neutral	None	None	None	None	N
E/G	0.4557	ambiguous	0.3737	ambiguous	-1.034	Destabilizing	0.969	D	0.487	neutral	N	0.475485756	None	None	N
E/H	0.7445	likely_pathogenic	0.6816	pathogenic	-0.83	Destabilizing	0.999	D	0.496	neutral	None	None	None	None	N
E/I	0.6528	likely_pathogenic	0.6035	pathogenic	-0.049	Destabilizing	0.973	D	0.554	neutral	None	None	None	None	N
E/K	0.3313	likely_benign	0.3008	benign	-0.234	Destabilizing	0.969	D	0.558	neutral	N	0.480816827	None	None	N
E/L	0.6986	likely_pathogenic	0.6363	pathogenic	-0.049	Destabilizing	0.91	D	0.543	neutral	None	None	None	None	N
E/M	0.7078	likely_pathogenic	0.6529	pathogenic	0.398	Stabilizing	0.998	D	0.563	neutral	None	None	None	None	N
E/N	0.4143	ambiguous	0.3348	benign	-0.546	Destabilizing	0.986	D	0.515	neutral	None	None	None	None	N
E/P	0.992	likely_pathogenic	0.9867	pathogenic	-0.266	Destabilizing	0.998	D	0.518	neutral	None	None	None	None	N
E/Q	0.2674	likely_benign	0.2352	benign	-0.494	Destabilizing	0.991	D	0.547	neutral	N	0.477730807	None	None	N
E/R	0.5807	likely_pathogenic	0.5236	ambiguous	-0.093	Destabilizing	0.993	D	0.522	neutral	None	None	None	None	N
E/S	0.4019	ambiguous	0.3444	ambiguous	-0.777	Destabilizing	0.953	D	0.533	neutral	None	None	None	None	N
E/T	0.3421	ambiguous	0.2898	benign	-0.559	Destabilizing	0.953	D	0.485	neutral	None	None	None	None	N
E/V	0.4583	ambiguous	0.408	ambiguous	-0.266	Destabilizing	0.1	N	0.349	neutral	D	0.569572604	None	None	N
E/W	0.9801	likely_pathogenic	0.9692	pathogenic	-0.466	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
E/Y	0.8362	likely_pathogenic	0.7849	pathogenic	-0.401	Destabilizing	0.993	D	0.593	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.