TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8117	24574;24575;24576	chr2:178718851;178718850;178718849	chr2:179583578;179583577;179583576
N2AB	7800	23623;23624;23625	chr2:178718851;178718850;178718849	chr2:179583578;179583577;179583576
N2A	6873	20842;20843;20844	chr2:178718851;178718850;178718849	chr2:179583578;179583577;179583576
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-66
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.49
• 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/D	None	None	0.999	N	0.505	0.39	0.269111216191	gnomAD-4.0.0	1.59135E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	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
E/A	0.2387	likely_benign	0.2627	benign	-0.565	Destabilizing	0.999	D	0.673	neutral	N	0.493721407	None	None	N
E/C	0.9193	likely_pathogenic	0.9259	pathogenic	-0.459	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/D	0.4137	ambiguous	0.4596	ambiguous	-0.751	Destabilizing	0.999	D	0.505	neutral	N	0.494099801	None	None	N
E/F	0.8508	likely_pathogenic	0.8667	pathogenic	0.173	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/G	0.3968	ambiguous	0.4363	ambiguous	-0.9	Destabilizing	1.0	D	0.667	neutral	N	0.519031365	None	None	N
E/H	0.7425	likely_pathogenic	0.7587	pathogenic	0.271	Stabilizing	1.0	D	0.638	neutral	None	None	None	None	N
E/I	0.3554	ambiguous	0.3797	ambiguous	0.343	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
E/K	0.2895	likely_benign	0.3065	benign	-0.261	Destabilizing	0.999	D	0.652	neutral	N	0.490719213	None	None	N
E/L	0.4463	ambiguous	0.4622	ambiguous	0.343	Stabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
E/M	0.485	ambiguous	0.4983	ambiguous	0.432	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
E/N	0.5654	likely_pathogenic	0.601	pathogenic	-0.893	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
E/P	0.5101	ambiguous	0.5347	ambiguous	0.062	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/Q	0.1979	likely_benign	0.1995	benign	-0.748	Destabilizing	1.0	D	0.608	neutral	N	0.489847066	None	None	N
E/R	0.4779	ambiguous	0.5033	ambiguous	0.177	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
E/S	0.4363	ambiguous	0.4695	ambiguous	-1.126	Destabilizing	0.999	D	0.65	neutral	None	None	None	None	N
E/T	0.4272	ambiguous	0.4524	ambiguous	-0.839	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
E/V	0.2282	likely_benign	0.2409	benign	0.062	Stabilizing	1.0	D	0.717	prob.delet.	N	0.493912444	None	None	N
E/W	0.9592	likely_pathogenic	0.9632	pathogenic	0.463	Stabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
E/Y	0.7992	likely_pathogenic	0.8219	pathogenic	0.442	Stabilizing	1.0	D	0.681	prob.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.