TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19068	57427;57428;57429	chr2:178597968;178597967;178597966	chr2:179462695;179462694;179462693
N2AB	17427	52504;52505;52506	chr2:178597968;178597967;178597966	chr2:179462695;179462694;179462693
N2A	16500	49723;49724;49725	chr2:178597968;178597967;178597966	chr2:179462695;179462694;179462693
N2B	10003	30232;30233;30234	chr2:178597968;178597967;178597966	chr2:179462695;179462694;179462693
Novex-1	10128	30607;30608;30609	chr2:178597968;178597967;178597966	chr2:179462695;179462694;179462693
Novex-2	10195	30808;30809;30810	chr2:178597968;178597967;178597966	chr2:179462695;179462694;179462693
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-26
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.9568
• 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
I/M	None	None	0.001	N	0.209	0.06	0.266843984389	gnomAD-4.0.0	1.59212E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85959E-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
I/A	0.0896	likely_benign	0.0876	benign	-0.298	Destabilizing	None	N	0.096	neutral	None	None	None	None	I
I/C	0.4496	ambiguous	0.4609	ambiguous	-0.637	Destabilizing	0.356	N	0.392	neutral	None	None	None	None	I
I/D	0.4574	ambiguous	0.3511	ambiguous	0.085	Stabilizing	0.038	N	0.478	neutral	None	None	None	None	I
I/E	0.3329	likely_benign	0.2513	benign	-0.019	Destabilizing	0.016	N	0.442	neutral	None	None	None	None	I
I/F	0.1488	likely_benign	0.153	benign	-0.532	Destabilizing	0.055	N	0.313	neutral	N	0.48311671	None	None	I
I/G	0.3192	likely_benign	0.3128	benign	-0.393	Destabilizing	0.007	N	0.43	neutral	None	None	None	None	I
I/H	0.3527	ambiguous	0.3341	benign	0.113	Stabilizing	0.356	N	0.456	neutral	None	None	None	None	I
I/K	0.2325	likely_benign	0.1844	benign	-0.017	Destabilizing	0.016	N	0.441	neutral	None	None	None	None	I
I/L	0.0928	likely_benign	0.0948	benign	-0.186	Destabilizing	0.001	N	0.199	neutral	N	0.466012541	None	None	I
I/M	0.0728	likely_benign	0.0732	benign	-0.278	Destabilizing	0.001	N	0.209	neutral	N	0.462414875	None	None	I
I/N	0.1762	likely_benign	0.1532	benign	0.095	Stabilizing	None	N	0.199	neutral	N	0.476381463	None	None	I
I/P	0.4963	ambiguous	0.5263	ambiguous	-0.193	Destabilizing	0.072	N	0.548	neutral	None	None	None	None	I
I/Q	0.2518	likely_benign	0.2205	benign	-0.109	Destabilizing	0.072	N	0.549	neutral	None	None	None	None	I
I/R	0.2028	likely_benign	0.1758	benign	0.407	Stabilizing	0.072	N	0.552	neutral	None	None	None	None	I
I/S	0.1262	likely_benign	0.1173	benign	-0.315	Destabilizing	None	N	0.123	neutral	N	0.42799287	None	None	I
I/T	0.0863	likely_benign	0.0837	benign	-0.315	Destabilizing	0.012	N	0.343	neutral	N	0.471378288	None	None	I
I/V	0.0593	likely_benign	0.0617	benign	-0.193	Destabilizing	None	N	0.073	neutral	N	0.465145749	None	None	I
I/W	0.6968	likely_pathogenic	0.7072	pathogenic	-0.557	Destabilizing	0.864	D	0.437	neutral	None	None	None	None	I
I/Y	0.4297	ambiguous	0.4266	ambiguous	-0.269	Destabilizing	0.356	N	0.435	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.