TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3870	11833;11834;11835	chr2:178741625;178741624;178741623	chr2:179606352;179606351;179606350
N2AB	3553	10882;10883;10884	chr2:178741625;178741624;178741623	chr2:179606352;179606351;179606350
N2A	None	None	chr2:None	chr2:None
N2B	3507	10744;10745;10746	chr2:178741625;178741624;178741623	chr2:179606352;179606351;179606350
Novex-1	3632	11119;11120;11121	chr2:178741625;178741624;178741623	chr2:179606352;179606351;179606350
Novex-2	3699	11320;11321;11322	chr2:178741625;178741624;178741623	chr2:179606352;179606351;179606350
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-27
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.2323
• 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
F/S	None	None	0.055	N	0.607	0.235	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
F/A	0.3734	ambiguous	0.4092	ambiguous	-0.901	Destabilizing	0.031	N	0.591	neutral	None	None	None	None	N
F/C	0.2508	likely_benign	0.3149	benign	-0.009	Destabilizing	0.828	D	0.599	neutral	N	0.50887602	None	None	N
F/D	0.6304	likely_pathogenic	0.6666	pathogenic	0.601	Stabilizing	0.038	N	0.61	neutral	None	None	None	None	N
F/E	0.6922	likely_pathogenic	0.7104	pathogenic	0.567	Stabilizing	None	N	0.491	neutral	None	None	None	None	N
F/G	0.6697	likely_pathogenic	0.6945	pathogenic	-1.098	Destabilizing	0.136	N	0.609	neutral	None	None	None	None	N
F/H	0.4856	ambiguous	0.537	ambiguous	0.191	Stabilizing	None	N	0.421	neutral	None	None	None	None	N
F/I	0.1925	likely_benign	0.201	benign	-0.401	Destabilizing	0.029	N	0.462	neutral	N	0.458613044	None	None	N
F/K	0.7162	likely_pathogenic	0.7344	pathogenic	0.08	Stabilizing	0.038	N	0.608	neutral	None	None	None	None	N
F/L	0.7997	likely_pathogenic	0.8045	pathogenic	-0.401	Destabilizing	None	N	0.263	neutral	N	0.449781762	None	None	N
F/M	0.5155	ambiguous	0.5217	ambiguous	-0.224	Destabilizing	0.12	N	0.557	neutral	None	None	None	None	N
F/N	0.5044	ambiguous	0.528	ambiguous	0.222	Stabilizing	0.072	N	0.635	neutral	None	None	None	None	N
F/P	0.892	likely_pathogenic	0.9162	pathogenic	-0.548	Destabilizing	0.356	N	0.623	neutral	None	None	None	None	N
F/Q	0.6625	likely_pathogenic	0.6887	pathogenic	0.115	Stabilizing	0.072	N	0.633	neutral	None	None	None	None	N
F/R	0.5541	ambiguous	0.5926	pathogenic	0.55	Stabilizing	0.072	N	0.634	neutral	None	None	None	None	N
F/S	0.2121	likely_benign	0.2367	benign	-0.411	Destabilizing	0.055	N	0.607	neutral	N	0.442065511	None	None	N
F/T	0.3117	likely_benign	0.3423	ambiguous	-0.352	Destabilizing	0.072	N	0.598	neutral	None	None	None	None	N
F/V	0.1952	likely_benign	0.2038	benign	-0.548	Destabilizing	0.012	N	0.532	neutral	N	0.443940194	None	None	N
F/W	0.4661	ambiguous	0.5264	ambiguous	-0.376	Destabilizing	0.356	N	0.571	neutral	None	None	None	None	N
F/Y	0.1583	likely_benign	0.1891	benign	-0.3	Destabilizing	None	N	0.271	neutral	N	0.38412819	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.