TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14304	43135;43136;43137	chr2:178633449;178633448;178633447	chr2:179498176;179498175;179498174
N2AB	12663	38212;38213;38214	chr2:178633449;178633448;178633447	chr2:179498176;179498175;179498174
N2A	11736	35431;35432;35433	chr2:178633449;178633448;178633447	chr2:179498176;179498175;179498174
N2B	5239	15940;15941;15942	chr2:178633449;178633448;178633447	chr2:179498176;179498175;179498174
Novex-1	5364	16315;16316;16317	chr2:178633449;178633448;178633447	chr2:179498176;179498175;179498174
Novex-2	5431	16516;16517;16518	chr2:178633449;178633448;178633447	chr2:179498176;179498175;179498174
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-93
• Domain position: 74
• Structural Position: 159
• Q(SASA): 0.4212
• 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
G/D	None	None	0.997	D	0.77	0.434	0.348324211639	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
G/A	0.2719	likely_benign	0.2208	benign	-0.225	Destabilizing	0.977	D	0.598	neutral	D	0.621102892	None	None	N
G/C	0.5633	ambiguous	0.4828	ambiguous	-0.76	Destabilizing	1.0	D	0.787	deleterious	D	0.764499249	None	None	N
G/D	0.3653	ambiguous	0.3032	benign	-0.931	Destabilizing	0.997	D	0.77	deleterious	D	0.613997016	None	None	N
G/E	0.3531	ambiguous	0.2879	benign	-1.107	Destabilizing	0.995	D	0.729	prob.delet.	None	None	None	None	N
G/F	0.8067	likely_pathogenic	0.742	pathogenic	-1.06	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
G/H	0.5864	likely_pathogenic	0.5148	ambiguous	-0.464	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
G/I	0.5588	ambiguous	0.4605	ambiguous	-0.429	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
G/K	0.5053	ambiguous	0.4027	ambiguous	-0.842	Destabilizing	0.635	D	0.515	neutral	None	None	None	None	N
G/L	0.6137	likely_pathogenic	0.5281	ambiguous	-0.429	Destabilizing	0.995	D	0.746	deleterious	None	None	None	None	N
G/M	0.7151	likely_pathogenic	0.6305	pathogenic	-0.416	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
G/N	0.433	ambiguous	0.3451	ambiguous	-0.412	Destabilizing	0.995	D	0.813	deleterious	None	None	None	None	N
G/P	0.9334	likely_pathogenic	0.9231	pathogenic	-0.33	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
G/Q	0.4105	ambiguous	0.3426	ambiguous	-0.752	Destabilizing	0.995	D	0.779	deleterious	None	None	None	None	N
G/R	0.3639	ambiguous	0.3102	benign	-0.316	Destabilizing	0.413	N	0.561	neutral	D	0.622022145	None	None	N
G/S	0.1684	likely_benign	0.1442	benign	-0.476	Destabilizing	0.993	D	0.773	deleterious	D	0.60641641	None	None	N
G/T	0.4155	ambiguous	0.3323	benign	-0.599	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
G/V	0.4661	ambiguous	0.379	ambiguous	-0.33	Destabilizing	0.997	D	0.753	deleterious	D	0.654228431	None	None	N
G/W	0.7677	likely_pathogenic	0.7225	pathogenic	-1.203	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
G/Y	0.7402	likely_pathogenic	0.666	pathogenic	-0.864	Destabilizing	1.0	D	0.789	deleterious	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.