TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27499	82720;82721;82722	chr2:178563637;178563636;178563635	chr2:179428364;179428363;179428362
N2AB	25858	77797;77798;77799	chr2:178563637;178563636;178563635	chr2:179428364;179428363;179428362
N2A	24931	75016;75017;75018	chr2:178563637;178563636;178563635	chr2:179428364;179428363;179428362
N2B	18434	55525;55526;55527	chr2:178563637;178563636;178563635	chr2:179428364;179428363;179428362
Novex-1	18559	55900;55901;55902	chr2:178563637;178563636;178563635	chr2:179428364;179428363;179428362
Novex-2	18626	56101;56102;56103	chr2:178563637;178563636;178563635	chr2:179428364;179428363;179428362
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-88
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.3808
• 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
T/S	rs1366798233	None	None	N	0.273	0.091	0.134241683229	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/S	rs1366798233	None	None	N	0.273	0.091	0.134241683229	gnomAD-4.0.0	1.23941E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.69524E-05	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
T/A	0.0521	likely_benign	0.0501	benign	-0.586	Destabilizing	None	N	0.276	neutral	N	0.366213693	None	None	I
T/C	0.2771	likely_benign	0.2905	benign	-0.2	Destabilizing	0.041	N	0.599	neutral	None	None	None	None	I
T/D	0.3608	ambiguous	0.3752	ambiguous	-0.268	Destabilizing	0.001	N	0.408	neutral	None	None	None	None	I
T/E	0.2876	likely_benign	0.3081	benign	-0.325	Destabilizing	0.001	N	0.389	neutral	None	None	None	None	I
T/F	0.2751	likely_benign	0.2985	benign	-0.926	Destabilizing	0.008	N	0.546	neutral	None	None	None	None	I
T/G	0.1596	likely_benign	0.1652	benign	-0.77	Destabilizing	None	N	0.385	neutral	None	None	None	None	I
T/H	0.2829	likely_benign	0.2864	benign	-1.124	Destabilizing	0.116	N	0.615	neutral	None	None	None	None	I
T/I	0.2059	likely_benign	0.2257	benign	-0.205	Destabilizing	0.001	N	0.449	neutral	N	0.466455258	None	None	I
T/K	0.2436	likely_benign	0.265	benign	-0.554	Destabilizing	0.001	N	0.39	neutral	None	None	None	None	I
T/L	0.1122	likely_benign	0.1256	benign	-0.205	Destabilizing	None	N	0.346	neutral	None	None	None	None	I
T/M	0.0891	likely_benign	0.0974	benign	0.239	Stabilizing	0.018	N	0.583	neutral	None	None	None	None	I
T/N	0.1148	likely_benign	0.1158	benign	-0.316	Destabilizing	0.001	N	0.428	neutral	N	0.459547928	None	None	I
T/P	0.6825	likely_pathogenic	0.7171	pathogenic	-0.302	Destabilizing	None	N	0.316	neutral	N	0.519500309	None	None	I
T/Q	0.2523	likely_benign	0.2627	benign	-0.614	Destabilizing	0.002	N	0.471	neutral	None	None	None	None	I
T/R	0.2101	likely_benign	0.2256	benign	-0.218	Destabilizing	0.002	N	0.469	neutral	None	None	None	None	I
T/S	0.0728	likely_benign	0.0707	benign	-0.533	Destabilizing	None	N	0.273	neutral	N	0.307626749	None	None	I
T/V	0.1191	likely_benign	0.1255	benign	-0.302	Destabilizing	None	N	0.313	neutral	None	None	None	None	I
T/W	0.683	likely_pathogenic	0.7168	pathogenic	-0.872	Destabilizing	0.316	N	0.619	neutral	None	None	None	None	I
T/Y	0.3447	ambiguous	0.3571	ambiguous	-0.626	Destabilizing	0.018	N	0.563	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.